[{"id":"absorbed-dose-term","kind":"term","name":"Absorbed dose and the gray (Gy)","aka":[],"tldr":"A measure of how much radiation energy actually landed in a piece of tissue, not how radioactive the source was. It is what determines whether a tumour or an organ is actually being treated or harmed.","summary":"Absorbed dose (symbol D) is the mean energy imparted by ionising radiation to a mass of matter, divided by that mass: D = dε/dm. Its SI unit is the gray (Gy), defined as one joule of absorbed energy per kilogram of tissue (1 Gy = 1 J/kg); the older unit, the rad, equals 0.01 Gy. Absorbed dose is a purely physical quantity, defined for a point, organ, tissue or the whole body, and it applies equally to external-beam radiotherapy and to radiation delivered internally by a radiopharmaceutical.\n\nIn radiopharmaceutical therapy, absorbed dose to tumours and organs at risk (typically kidneys, salivary glands and bone marrow for PSMA and SSTR-targeted agents) is estimated from serial quantitative imaging using the MIRD formalism, and it is the physical quantity that dosimetry-guided treatment tries to optimise: enough gray to the tumour, not too much to the kidneys or marrow. It is distinct from equivalent dose and effective dose (measured in sievert), which apply a biological weighting on top of absorbed dose for radiation protection purposes; for prescribing and evaluating radiopharmaceutical therapy, absorbed dose in gray to the organ or tumour of interest, not sievert, is the clinically relevant quantity.\n\nBecause different radiation types (alpha, beta, gamma) deposit their energy very differently at the microscopic scale even at the same absorbed dose, gray alone does not fully capture biological effect; that is the role of linear energy transfer and relative biological effectiveness.","asOf":"2026-09-22","links":[{"label":"BIPM: Resolution 9 of the 15th CGPM (1975), adoption of the gray","url":"https://www.bipm.org/en/-/resolution-cgpm-15-9"},{"label":"ICRU Report 85a via IAEA/ICTP teaching slides: definition of absorbed dose","url":"https://indico.ictp.it/event/10205/session/2/contribution/4/material/slides/0.pdf"}],"tags":[],"related":["equivalent-dose","mird-formalism","linear-energy-transfer"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","in-vivo-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"dosimetry"},{"id":"activity-prescription","kind":"term","name":"Activity prescription: fixed versus dosimetry-guided dosing","aka":[],"tldr":"Deciding how much radioactive drug to give a patient. Most approved radioligand therapies today use the same fixed amount for everyone, but some clinics instead measure each patient's own radiation exposure and adjust the amount up or down to try to give more benefit with less harm.","summary":"Activity prescription is the process of deciding how much radioactivity (in gigabecquerel or millicurie) to administer per cycle of a radiopharmaceutical therapy, and how many cycles to give. Two broad approaches are used. Fixed (empirical) activity prescription gives every eligible patient the same standard activity per cycle, as established in the pivotal trials: 177Lu-PSMA-617 (Pluvicto) is approved and administered as 7.4 GBq (200 mCi) every six weeks for up to six cycles, as tested in the VISION trial, and 177Lu-dotatate (Lutathera) as a fixed 7.4 GBq per cycle for four cycles, as tested in NETTER-1, with dose reductions on toxicity but no upward personalisation. Regulators have approved these regimens without requiring patient-specific dosimetry for in-label use.\n\nDosimetry-guided (personalised) activity prescription instead measures each patient's own absorbed dose to organs at risk (chiefly kidneys and, for PSMA agents, salivary glands, and bone marrow for both) from an early cycle, using serial quantitative imaging and the MIRD formalism, and then adjusts subsequent cycle activity, or the number of cycles, to approach an organ dose-tolerance threshold (commonly cited working limits are around 23 Gy cumulative to the kidneys and around 2 Gy to red marrow) rather than stopping at a fixed number of fixed-size doses. Reported mean absorbed doses per unit administered activity vary widely between patients (for example roughly 0.4-1.9 Gy/GBq to salivary glands and roughly 0.4-1.0 Gy/GBq to kidneys for 177Lu-PSMA agents), which is the empirical basis for the argument that a single fixed activity under- or over-treats a substantial fraction of patients.\n\nDosimetry-guided prescription is used selectively in academic centres and in some national protocols, and is an active area of clinical trial development (see the idea of dosimetry-personalised PRRT instead of four fixed cycles), but it is more resource-intensive, requiring multiple post-therapy scans, quantitative calibration and physicist time, and has not replaced fixed dosing as the regulatory standard for the approved indications.","asOf":"2026-09-22","links":[{"label":"PMC: joint EANM/SNMMI procedure guideline for 177Lu-labelled PSMA radioligand therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10317889/"},{"label":"PMC: dosimetry in radiopharmaceutical therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12079709/"}],"tags":[],"related":["mird-formalism","time-activity-curve","becquerel-curie","lu-177"],"indications":[],"sections":[],"technologies":["lu177-radioligand-therapy","prrt","radioligand-dosimetry","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"dosimetry"},{"id":"alara","kind":"term","name":"ALARA (as low as is reasonably achievable)","aka":[],"tldr":"A rule that radiation should always be kept as low as practically possible, not just below the legal limit, taking into account cost, technology and benefit.","summary":"ALARA (as low as is reasonably achievable) is defined in US Nuclear Regulatory Commission regulations (10 CFR 20.1003) as making every reasonable effort to maintain radiation exposures as far below the dose limits in 10 CFR Part 20 as is practical, taking into account the state of technology, the economics of improvements in relation to that technology and to benefits for public health and safety, and other societal and socioeconomic considerations, all in the context of using nuclear energy and licensed materials in the public interest. It is not itself a numeric dose limit; it is an operating principle that sits below the hard limits and requires continual effort to reduce doses further wherever reasonably practical.\n\n10 CFR 20.1101 requires every licensee to develop, document and implement a radiation protection programme that is commensurate with the scope and extent of licensed activities and sufficient to ensure compliance, with ALARA as its guiding principle for both occupational and public exposure. In a nuclear medicine or radiopharmacy setting this translates into concrete practice: shielding (lead or tungsten syringe shields, L-blocks, hot-cell walls), distance (using tongs or automated dispensers rather than close manual handling), time (minimising time spent near unshielded sources), workflow design that keeps the highest-activity work furthest from staff and the public, and engineering controls such as ventilated hoods for volatile radiopharmaceuticals.\n\nALARA is distinct from, but complementary to, the specific dose limits in Part 20 (for example, 100 mrem/year for members of the public, or 2 mrem in any one hour in unrestricted areas) and the training-and-equipment requirements of Part 35 for medical use of byproduct material; a facility can be within all numeric limits and still be found non-compliant if it has not made the reasonable further efforts ALARA demands, particularly during periodic radiation safety programme reviews and inspections.","asOf":"2026-09-22","links":[{"label":"10 CFR 20.1003, Definitions - ALARA (NRC eCFR)","url":"https://www.nrc.gov/reading-rm/doc-collections/cfr/part020/part020-1003.html"},{"label":"eCFR: 10 CFR Part 20, Standards for Protection Against Radiation","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-20"}],"tags":["NRC","radiation protection","10 CFR Part 20"],"related":["radiation-safety-officer","hot-lab","dose-calibrator","authorized-user","gamma-probes-dose-calibrators"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation"},{"id":"alpha-vs-beta","kind":"term","name":"Alpha vs beta emitters","aka":[],"tldr":"Beta particles (lutetium-177) travel millimetres and are good for bulky disease; alpha particles (actinium-225) travel a few cells' width and kill with far higher energy.","summary":"This is about alpha particles versus beta particles in radioligand therapy, not the alpha/beta ratio of the linear-quadratic model used in external-beam fractionation. Beta and alpha emitters are the two kinds of particle used in radioligand therapy. Beta particles from lutetium-177 have low linear energy transfer and a range of 1 to 10 mm, so their crossfire helps in heterogeneous bulky tumours at the cost of marrow toxicity. Alpha particles from actinium-225 have very high linear energy transfer, around 100 keV per micrometre, travel only 50 to 100 micrometres and cause oxygen-independent DNA breaks, though daughter recoil redistributes dose and actinium-225 supply is the bottleneck. The distinction underlies the Radioligand therapy (beta emitters) and Targeted alpha therapy technologies and the pairing Beta radioligand to alpha radioligand, and it is referenced by Radium-223 dichloride and the Neuroendocrine tumours entry.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Targeted_alpha-particle_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Targeted_alpha-particle_therapy"}],"tags":[],"related":["lu-177","ac-225","ra-223"],"indications":[],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"anaemia","kind":"term","name":"Anaemia","aka":["anemia","anaemic","anemic","low haemoglobin","low hemoglobin","haemoglobin","hemoglobin","transfusion-dependent","transfusion dependence","transfusion independence","red cell transfusion","erythropoiesis-stimulating agent","ESA","ESAs","iron deficiency","erythropoiesis-stimulating agents"],"tldr":"A shortage of red blood cells or haemoglobin, causing tiredness and breathlessness. In cancer it comes from the disease itself (marrow infiltration, bleeding, inflammation), from chemotherapy suppressing the marrow, and from some targeted drugs.","summary":"Present in 30-90% of patients depending on cancer and treatment; a defining feature of myeloma, MDS and leukaemia, and the dose-limiting toxicity of PARP inhibitors (olaparib, talazoparib) and of some ADCs and radioligands. Managed by treating the cause, iron replacement, red cell transfusion (with restrictive thresholds) and, cautiously, erythropoiesis-stimulating agents, which raise thrombosis risk and were linked to worse outcomes when used to high targets. Transfusion independence is an endpoint in MDS trials (luspatercept, imetelstat). Fatigue from anaemia is one of the most common and under-treated symptoms in oncology.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Anemia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Anemia"}],"tags":[],"related":["cytopenias","thrombocytopenia"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"arpi","kind":"term","name":"Androgen receptor pathway inhibitor (ARPI)","aka":["ARPI","ARPIs","ARSI","androgen receptor signalling inhibitor","androgen receptor pathway inhibitor","novel hormonal agent","NHA","next-generation antiandrogen","second-generation antiandrogen","AR antagonist","AR inhibitor","antiandrogen","anti-androgen","AR-V7","AR-targeted","AR antagonists"],"tldr":"The newer prostate cancer hormone pills (abiraterone, enzalutamide, apalutamide, darolutamide) that block the androgen receptor or the last steps of androgen production, used on top of standard testosterone suppression.","summary":"Abiraterone blocks CYP17 androgen synthesis (given with prednisone); enzalutamide, apalutamide and darolutamide are potent AR antagonists. Adding an ARPI to ADT extends survival in metastatic hormone-sensitive disease (LATITUDE, ARCHES, TITAN, ARASENS), in non-metastatic castration-resistant disease and in castration-resistant disease before or after docetaxel. Resistance arises via AR amplification, ligand-binding domain mutations, the AR-V7 splice variant and lineage plasticity to neuroendocrine disease; switching ARPIs after failure gives little benefit, so PSMA radioligands, PARP inhibitors and chemotherapy follow. Older antiandrogens (bicalutamide) are weaker first-generation drugs.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Antiandrogen","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antiandrogen"}],"tags":[],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["abiraterone","enzalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"antigen","kind":"term","name":"Antigen","aka":["antigens","tumour antigen","tumour antigens","tumor antigen","tumor antigens","target antigen","target antigens","antigenic","tumour-associated antigen","tumour-associated antigens","tumor-associated antigen","tumor-associated antigens","antigen-negative","antigen loss"],"tldr":"Anything an antibody or immune cell can recognise, typically a protein on a cell's surface. In cancer, an antigen is the flag that tells a drug or an immune cell 'this is the cell to attack'.","summary":"Most cancer antigens are ordinary human proteins that a tumour makes in unusual amounts (HER2, TROP2, CD19, PSMA), so drugs targeting them also touch normal cells that carry a little; truly tumour-specific antigens arise from mutations (neoantigens) or from viral proteins. A good drug antigen is abundant on tumour cells, scarce on essential normal tissue, and stable over time. Tumours escape by losing the antigen, which is how CD19-negative relapse defeats CAR-T, and by hiding the pieces of antigen they would normally display to T cells.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Antigen","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antigen"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":["her2","trop2","psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"attenuation-correction","kind":"term","name":"Attenuation correction","aka":[],"tldr":"Radiation coming from deep inside the body has to pass through more tissue to reach the scanner's detectors than radiation from near the skin, so without correction, deep organs look falsely dim. Attenuation correction uses a separate scan (usually a CT) to fix this and make the image quantitatively accurate.","summary":"Attenuation is the loss of PET or SPECT signal that occurs when photons emitted inside the body are absorbed or scattered before they escape and reach the detector; because photons emitted deep in the body must traverse more tissue than those emitted near the surface, uncorrected images make deep structures appear falsely cold and superficial tissue falsely hot. Attenuation correction is the processing step that compensates for this, turning PET or SPECT from a qualitative picture into a quantitatively meaningful measurement of activity concentration, the basis for standardised uptake value (SUV) and for dosimetry calculations.\n\nIn PET, an annihilation event produces two 511 keV photons travelling in opposite directions; because attenuation depends on the total tissue thickness traversed by both photons along their combined path (the line of response), the attenuation correction factor for that path can be computed independent of exactly where along the path the decay occurred, making PET attenuation correction mathematically straightforward once the tissue attenuation map is known. In modern PET/CT and SPECT/CT, this attenuation map is derived from the CT scan: the CT's x-ray attenuation values (measured at a low, polyenergetic effective energy around 70 keV) must be mathematically rescaled to the much higher, monoenergetic energy of the emission photons (511 keV for PET, the specific gamma energy for a given SPECT radionuclide, such as 208 keV for 177Lu) before being applied as a correction, since attenuation is strongly energy-dependent.\n\nAttenuation correction is one of the largest and most consequential physical corrections applied to PET and SPECT data, essential for accurate SUV measurement, lesion detectability, and any dosimetry that depends on absolute activity quantification; historically it was performed with a rotating external radioactive transmission source before CT-based methods became standard.","asOf":"2026-09-22","links":[{"label":"AAPM (Kinahan): CT-based attenuation correction (CTAC), artifacts, and quantitation in PET/CT","url":"https://www.aapm.org/meetings/08ss/documents/Kinahan.pdf"},{"label":"PMC: attenuation correction in emission tomography using synergistic PET/MR data","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4715007/"}],"tags":[],"related":["partial-volume-effect","suv","time-of-flight-pet","lu-177"],"indications":[],"sections":[],"technologies":["pet-ct","spect-ct","pet","spect","quantitative-imaging-biomarkers"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics"},{"id":"authorized-user","kind":"term","name":"Authorized User (AU)","aka":[],"tldr":"In the US, only a physician who has completed specific radiation training and case experience, and who is named on the clinic's license, is legally allowed to order and give radioactive drugs to patients.","summary":"An Authorized User (AU) is a physician, dentist or podiatrist who meets US Nuclear Regulatory Commission training-and-experience requirements under 10 CFR Part 35 and is named as such on a specific medical-use license (or an equivalent permit). Only AUs, and authorized nuclear pharmacists preparing material under their direction, may prescribe or administer byproduct material to patients in the practice of medicine; every administration must follow either an individually written prescription from an AU or a licensee-approved written protocol.\n\nThe requirements differ by category of use. For imaging and localisation studies not requiring a written directive (10 CFR 35.290, covering diagnostic PET and SPECT tracers), a physician needs 700 hours of training and experience including a minimum of 80 hours of classroom and laboratory instruction in radiation physics, protection, mathematics of radioactivity, chemistry of byproduct material and radiation biology, plus supervised work experience covering ordering and receiving radioactive material, dose-calibrator quality control, dosage calculation, and eluting generators. For uses requiring a written directive (10 CFR 35.390, covering therapeutic radiopharmaceuticals such as lutetium-177 or iodine-131 therapy), the bar is higher: 700 hours of training including a minimum of 200 hours of classroom and laboratory work, plus supervised experience administering at least three cases in each dosage category for which authorisation is sought (for example, specific activity thresholds of oral sodium iodide-131). Board certification by a recognised specialty board (such as the American Board of Nuclear Medicine or American Board of Radiology) can substitute for the itemised hour requirements if the certifying board's own process covers the same content and includes an examination.\n\nAn AU already qualified under 35.390 for therapeutic use can add 35.290 diagnostic authorisation with a smaller increment of generator-elution experience, recognising the overlapping physics and safety curriculum. All training and experience must have been obtained within the seven years preceding the license application, or be supported by continuing education and experience since. Individual attestation is provided by a preceptor AU or a residency programme director, and the NRC or Agreement State reviews the credentials before amending the license; the NRC does not issue any credential directly to the individual.","asOf":"2026-09-22","links":[{"label":"10 CFR 35.290, Training for imaging and localization studies (Cornell LII)","url":"https://www.law.cornell.edu/cfr/text/10/35.290"},{"label":"10 CFR 35.390, Training for use of unsealed byproduct material for which a written directive is required (Cornell LII)","url":"https://www.law.cornell.edu/cfr/text/10/35.390"},{"label":"NRC: Authorized Individuals - definitions and license amendment process","url":"https://www.nrc.gov/materials/miau/med-use-toolkit/auth-individuals"}],"tags":["NRC","10 CFR Part 35","physician credentialing"],"related":["radiation-safety-officer","nrc-licensing","hot-lab","dose-calibrator","release-criteria","lu-177","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation"},{"id":"becquerel-curie","kind":"term","name":"Becquerel and curie (units of radioactivity)","aka":[],"tldr":"The two units used to state how radioactive something is. The becquerel (the modern, official unit) counts one radioactive decay per second; the curie (the older unit, still common in the United States) equals 37 billion decays per second.","summary":"Activity, the rate at which a radioactive sample decays, is measured in becquerels (Bq), the SI unit, where 1 Bq equals one nuclear disintegration per second. The older, non-SI unit is the curie (Ci), originally based on the activity of one gram of radium-226 and now defined by exact convention as 1 Ci = 3.7 x 10^10 Bq (37 gigabecquerels). The becquerel officially replaced the curie in the International System of Units in 1975, but the curie (and its submultiples, millicurie and microcurie) remains in everyday clinical use in the United States, while most of the rest of the world uses becquerel and its multiples (kBq, MBq, GBq).\n\nBecause radiopharmaceutical doses span many orders of magnitude, from microcurie/kilobecquerel amounts of injected tracer mass to gigabecquerel/multi-hundred-millicurie therapeutic activities, the two unit systems are used side by side in practice: a typical PET tracer dose is quoted as roughly 185-370 MBq (5-10 mCi), while a typical cycle of lutetium-177 radioligand therapy is prescribed as 7.4 GBq (200 mCi). Converting between them uses the fixed factor 1 Ci = 37 GBq, so 1 mCi = 37 MBq and 1 MBq is about 0.027 mCi.\n\nActivity (Bq or Ci) is not the same as absorbed dose (measured in gray) or equivalent/effective dose (measured in sievert): activity describes the source, while gray and sievert describe the energy actually deposited in tissue.","asOf":"2026-09-22","links":[{"label":"BIPM/Wikipedia: becquerel, SI unit of activity","url":"https://en.wikipedia.org/wiki/Becquerel"},{"label":"Wikipedia: curie, definition and conversion to becquerels","url":"https://en.wikipedia.org/wiki/Curie_(unit)"}],"tags":[],"related":["absorbed-dose-term","activity-prescription","lu-177"],"indications":[],"sections":[],"technologies":["radioligand-therapy","lu177-radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics"},{"id":"biochemical-recurrence","kind":"term","name":"Biochemical recurrence (BCR)","aka":[],"tldr":"PSA rising again after surgery or radiation, usually years before anything shows on a scan.","summary":"Biochemical recurrence is a rising PSA after treatment for prostate cancer, usually years before anything is visible on a scan. It is defined as a PSA of 0.2 ng/mL or more after prostatectomy, or a rise of 2 ng/mL above the nadir after radiation. PSMA PET, with agents such as fluciclovine F-18 and Illuccix, can now find the recurrent disease at very low PSA levels in most men, opening the way to salvage radiation or metastasis-directed therapy. The EMBARK trial, reported in 2023, showed that enzalutamide with or without androgen deprivation delays metastasis in high-risk recurrence defined by a short PSA doubling time. The term is linked from the PSA entry and from ideas on PSMA-PET-guided metastasis-directed therapy and on localising residual disease.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Biochemical_recurrence","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biochemical_recurrence"}],"tags":[],"related":["f-18"],"indications":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["embark"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"biological-half-life","kind":"term","name":"Biological half-life","aka":[],"tldr":"The time it takes the body to clear out half of a substance through ordinary biological processes (metabolism and excretion), separate from any radioactive decay. A drug that the kidneys clear quickly has a short biological half-life regardless of which radioactive atom is attached to it.","summary":"Biological half-life is the time required for the amount of a substance present in an organ or the whole body to fall to half its original value through biological elimination processes alone, that is, metabolic breakdown, renal or hepatobiliary excretion, or other clearance mechanisms, independent of any radioactive decay of an attached isotope. It is a pharmacokinetic property of the molecule (and of the specific tissue considered), not of the radionuclide, and it is influenced by physiological factors such as renal function, hydration and hepatic clearance.\n\nBiological half-life is measured directly from a decay-corrected time-activity curve, or inferred from the biodistribution of a stable-isotope-labelled or otherwise trackable analogue of the compound. In radiopharmaceutical dosimetry it is combined with the physical (radioactive) half-life to give the effective half-life, which is the quantity that actually determines how quickly the radioactivity, and therefore the absorbed dose rate, declines in a given organ or tumour after administration.\n\nBecause biological half-life is independent of the isotope used, the same targeting molecule with different attached radionuclides (a diagnostic and a therapeutic pair) is expected to share very similar tissue biological half-lives, an assumption that underlies using a diagnostic imaging agent's kinetics (for example gallium-68 or copper-64 labelled) to predict dosimetry for its therapeutic counterpart (lutetium-177 or actinium-225 labelled) in theranostic pairs.","asOf":"2026-09-22","links":[{"label":"Radiopharmacy teaching notes (Loyola University Chicago): effective half-life","url":"https://www.lumen.luc.edu/lumen/meded/radio/nuc_med/radpharm/sect-a3.htm"},{"label":"DOE-HDBK-1122-99: radiological control technician training, biological half-life","url":"https://www.energy.gov/sites/prod/files/2013/07/f2/hdbk-1122-04_sg112_0.pdf"}],"tags":[],"related":["effective-half-life","half-life","time-activity-curve","ga-68","cu-64","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics"},{"id":"bone-marrow","kind":"term","name":"Bone marrow","aka":["marrow","bone-marrow","marrow suppression","myelosuppression","myelosuppressive","blood counts","blood count","low blood counts","neutropenia","neutropenic","anaemia","anemia","thrombocytopenia"],"tldr":"The soft tissue inside bones where all blood cells are made. Chemotherapy damages it, causing the low blood counts that limit how much treatment a patient can take.","summary":"Blood stem cells in the marrow produce billions of red cells, white cells and platelets each day; because they divide constantly, they are collateral damage for most chemotherapy and for some ADC payloads, radiotherapy to bone and radioligands. The consequences are anaemia (fatigue), neutropenia (infection risk, sometimes life-threatening) and thrombocytopenia (bleeding), which together are the commonest reason for dose delays and reductions. Growth factors such as G-CSF speed recovery of white cells, and a marrow biopsy is how leukaemias and myeloma are diagnosed and monitored.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Bone_marrow","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bone_marrow"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"bone-metastases","kind":"term","name":"Bone metastases and skeletal-related events","aka":["bone metastasis","skeletal metastases","skeletal-related events","skeletal-related event","SRE","bone-only","bone-predominant","osseous metastases","pathological fracture","spinal cord compression"],"tldr":"Cancer spread to the bones, most common in prostate, breast, lung, kidney and thyroid cancer and myeloma. It causes pain, fractures and high calcium, and the complications are counted in trials as 'skeletal-related events'.","summary":"Skeletal-related events (fracture, need for radiotherapy or surgery to bone, spinal cord compression, hypercalcaemia) are reduced 30-40% by bone-modifying agents (zoledronic acid, denosumab). Single-fraction 8 Gy radiotherapy relieves pain as well as longer courses; SBRT gives more durable relief for spine metastases. Bone-seeking radiopharmaceuticals (radium-223, strontium-89) treat bone-predominant prostate cancer, and bone-only disease has a better prognosis than visceral spread in breast cancer. Spinal cord compression is an emergency needing steroids and urgent radiotherapy or surgery.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Bone_metastasis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Bone_metastasis"}],"tags":[],"related":["ra-223","sr-89"],"indications":["prostate","rcc"],"sections":[],"technologies":[],"targets":[],"drugs":["radium-223"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Anatomy"},{"id":"chelator-term","kind":"term","name":"Chelator (bifunctional chelating agent)","aka":[],"tldr":"A molecular 'cage' that grips a radioactive metal atom tightly so it stays attached to the drug all the way to the tumour, instead of leaking out and going to the wrong part of the body.","summary":"A chelator (or bifunctional chelating agent, BFC/BFCA) is the part of a metal-based radiopharmaceutical that binds the radiometal ion in a stable coordination complex while a second reactive group lets it be covalently attached to a targeting molecule, such as a peptide, antibody or small molecule. The three-part architecture, radiometal plus chelator plus targeting vector (often via a linker), is the standard design of essentially all radiometal radiopharmaceuticals, from diagnostic 68Ga and 64Cu tracers to therapeutic 177Lu, 90Y and 225Ac agents.\n\nDOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) is the dominant macrocyclic chelator in the field, used with 68Ga, 111In, 86Y/90Y, 44Sc/47Sc and 177Lu, among others, because its rigid ring gives very high thermodynamic and kinetic stability once the metal is locked in; the trade-off is that labelling usually needs heating (60-95°C for 30-90 minutes), which limits its use with heat-sensitive biomolecules such as intact antibodies. Acyclic chelators (such as DTPA) and other macrocycles (such as NOTA, which forms a stable gallium-68 complex at room temperature) trade some of that ultimate stability for faster, milder labelling conditions.\n\nA poorly matched chelator-metal pair, or incomplete complexation, shows up as radiochemical impurity: unbound or loosely bound radiometal that redistributes in the body (free gallium-68 to bone, free lutetium-177 to bone and liver) rather than following the targeting vector, degrading image quality and increasing off-target dose. Chelator choice is therefore one of the first decisions in designing any new radiometal agent and is documented in the drug's CMC (chemistry, manufacturing and controls) package.","asOf":"2026-09-22","links":[{"label":"Chemical Society Reviews: matching chelators to radiometals for radiopharmaceuticals","url":"https://pubs.rsc.org/en/content/articlehtml/2014/cs/c3cs60304k"},{"label":"PMC: the chemical scaffold of theranostic radiopharmaceuticals","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9143622/"}],"tags":[],"related":["specific-activity","radiochemical-purity","ga-68","in-111","cu-64","sc-44","y-86","lu-177","ac-225","y-90"],"indications":[],"sections":[],"technologies":["site-specific-conjugation","radionuclide-generators-kits","pet-tracer-manufacturing"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"chemistry"},{"id":"complete-response-term","kind":"term","name":"Complete response (CR) and partial response (PR)","aka":["complete response","complete responses","complete remission","complete remissions","CR rate","CRi","CR/CRi","complete response rate","stringent complete response","sCR","partial response","partial responses","partial remission","PR rate","very good partial response","VGPR","stable disease","best response","best overall response","deep response","deep responses","complete response rates"],"tldr":"A complete response means every measurable trace of the cancer has disappeared on scans or in the marrow; a partial response means it has shrunk by at least 30% (RECIST) but is still there. Neither is the same as cure: microscopic disease can remain.","summary":"Solid tumour responses are defined by RECIST 1.1 (complete: all target lesions gone and nodes <10 mm; partial: ≥30% decrease in summed diameters; progressive: ≥20% increase or new lesions; stable: neither); lymphoma uses Lugano and PET; leukaemia uses marrow blast count and count recovery (CR, CRi for incomplete recovery); myeloma uses IMWG (stringent CR, VGPR, PR). Complete responses are the strongest single-arm signal and, when durable, drive accelerated approvals; the proportion of complete responders and the depth of response (MRD, ctDNA clearance) increasingly predict long-term outcome. In neoadjuvant settings pathological complete response is judged on the resected specimen, and clinical complete response guides organ preservation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Response_Evaluation_Criteria_in_Solid_Tumors","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Response_Evaluation_Criteria_in_Solid_Tumors"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"crossover","kind":"term","name":"Crossover in trials","aka":["cross-over","crossover-adjusted","crossover adjustment","adjusted for crossover","permitted crossover","crossover was permitted","crossover rate","post-progression therapy","subsequent therapy","subsequent treatment","RPSFT","rank-preserving structural failure time","IPCW","treatment switching","unplanned crossover","confounded by crossover"],"tldr":"When patients in a trial's control arm are allowed to switch to the experimental drug after their cancer progresses. It is fair to patients but blurs the survival comparison, because the control group has now had the drug too.","summary":"Crossover is common in trials of drugs already approved elsewhere or clearly active (imatinib in GIST, osimertinib in FLAURA, 177Lu-PSMA in VISION and PSMAfore, where 84% of controls crossed over) and explains why such trials often show large progression-free survival gains but little or no overall survival difference. Statistical corrections (rank-preserving structural failure time, inverse probability of censoring weighting) estimate what survival would have been without crossover but rely on assumptions and are treated cautiously by regulators, who may still demand an OS trend. In regulatory debates, crossover cuts both ways: it can hide a true survival benefit or excuse its absence.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Crossover_study","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Crossover_study"}],"tags":[],"related":["estimand","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["vision","psmafore","therap"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"cytopenias","kind":"term","name":"Cytopenias and myelosuppression","aka":["cytopenia","cytopenias","myelosuppression","myelosuppressive","bone marrow suppression","marrow suppression","marrow toxicity","haematological toxicity","hematological toxicity","haematologic toxicity","hematologic toxicity","pancytopenia","bicytopenia","lymphopenia","lymphocytopenia","prolonged cytopenias","late cytopenias","ICAHT","immune effector cell-associated haematotoxicity","count recovery","blood counts","full blood count","complete blood count","CBC"],"tldr":"The umbrella term for low blood counts of any kind (white cells, red cells, platelets) when treatment suppresses the bone marrow. Most chemotherapy causes it temporarily; radioligands, CAR-T and some pills cause longer-lasting versions.","summary":"Myelosuppression is the shared toxicity of cytotoxic chemotherapy, conditioning regimens, lymphodepletion, radioligand therapy (177Lu-PSMA, PRRT) and a range of targeted agents, graded per lineage by CTCAE; pancytopenia means all three lineages are low. Blood counts before each cycle gate treatment, and delays and dose reductions are the standard responses. After CAR-T, prolonged and biphasic cytopenias (ICAHT) affect a third of patients and drive infection deaths months after infusion; lymphopenia is a marker of poorer immunotherapy outcomes. Therapy-related MDS is the late, permanent form of marrow injury.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Myelosuppression","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Myelosuppression"}],"tags":[],"related":["thrombocytopenia","anaemia","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"deauville-for-pet","kind":"term","name":"Deauville five-point scale for PET","aka":[],"tldr":"A simple 1-to-5 score doctors use on a PET scan of lymphoma to say whether treatment is working, by comparing how bright the tumour looks against two normal reference areas: the blood in the chest and the liver.","summary":"The Deauville five-point scale (also called the 5-point scale, 5PS) grades FDG uptake in each lymphoma lesion visually against two internal reference tissues: the mediastinal blood pool and the liver. Score 1 is no uptake above background; 2 is uptake at or below the mediastinal blood pool; 3 is uptake above the mediastinum but at or below the liver; 4 is uptake moderately higher than liver; 5 is uptake markedly higher than liver and/or new lesions. An additional X denotes new uptake felt unlikely to be lymphoma. Proposed in 2009 and incorporated into the 2014 Lugano classification for staging and response assessment, it is now the standard scale for FDG-avid nodal lymphomas including Hodgkin lymphoma and most non-Hodgkin subtypes.\n\nUnder Lugano, a complete metabolic response is a Deauville score of 1, 2 or 3 (with or without a residual mass) and no marrow involvement; a partial metabolic response is score 4 or 5 with reduced uptake from baseline; no metabolic response (stable disease) is score 4 or 5 unchanged; progressive metabolic disease is score 4 or 5 with increasing uptake or new FDG-avid lesions. Score 3 is generally treated as a good-prognosis complete response, except in de-escalation trials, where some protocols treat score 3 as an inadequate interim response to avoid undertreatment.\n\nThe scale's simplicity and reproducibility drove its adoption in trials such as RATHL, which used interim PET response to de-escalate or intensify treatment in advanced Hodgkin lymphoma. A residual mass greater than 2 cm alongside a Deauville 1-2 result at end of treatment has been associated with a higher relapse risk in diffuse large B-cell lymphoma in some series, illustrating that the scale is read alongside anatomic findings rather than in isolation.","asOf":"2026-09-22","links":[{"label":"Radiopaedia: Deauville five-point scale","url":"https://radiopaedia.org/articles/deauville-five-point-scale?lang=us"},{"label":"Radiopaedia: Lugano classification (PET-CT treatment response)","url":"https://radiopaedia.org/articles/lugano-classification-pet-ct-treatment-response?lang=us"},{"label":"RATHL trial: adapted treatment guided by interim PET-CT in advanced Hodgkin lymphoma, NEJM 2016","url":"https://www.nejm.org/doi/10.1056/NEJMoa1510093"}],"tags":["response criteria","lymphoma","FDG PET"],"related":["fdg-pet","dlbcl","rathl","hd21","complete-response-term","suv"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"imaging"},{"id":"decay-correction","kind":"term","name":"Decay correction","aka":[],"tldr":"Adjusting a radioactivity measurement to account for the fact that the sample kept decaying between the moment it was measured and the moment you actually care about, such as when the dose was drawn up versus when it was injected, or between two scans taken hours apart.","summary":"Decay correction is the mathematical adjustment of a measured activity or image intensity to remove the effect of ongoing radioactive decay between the time of measurement and a chosen reference time, using the standard exponential decay law At = A0 x e^(-λt), where λ = ln(2)/T-half is the decay constant and t is the elapsed time. Without this correction, any comparison of activity across two different times, whether it is checking the activity in a dose calibrator against the time of patient injection, or comparing two frames of a dynamic PET scan, or comparing organ uptake on serial post-therapy SPECT images taken days apart, would confound genuine biological change with the trivial fact that the radionuclide has simply decayed further by the later time point.\n\nIn practice, decay correction is applied both to individual imaging frames (each PET or SPECT frame is corrected back to a common reference time, commonly either the frame start time, its mid-point, or the injection time) and to any activity measurement recorded away from the time it is needed, such as calculating the percentage of injected activity present in an organ, which requires decay-correcting the measured organ activity back to, or the injected activity forward to, a common time point. For dynamic and quantitative studies, the correction must also account for decay occurring during the frame acquisition itself, not just between frames, particularly for short-half-life radionuclides such as rubidium-82 or oxygen-15 relative to the scan duration.\n\nGetting the decay-correction convention wrong, or applying it inconsistently between the dose calibrator, the scanner and the dosimetry software, is a recognised, easily overlooked source of quantitative error in both diagnostic quantification (SUV, kinetic modelling) and therapeutic dosimetry.","asOf":"2026-09-22","links":[{"label":"IAEA Human Health Reports No. 9: quantitative nuclear medicine imaging, decay correction","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/Pub1605_web.pdf"},{"label":"Journal of Nuclear Medicine Technology: decay correction for quantitative myocardial PET perfusion","url":"https://tech.snmjournals.org/content/jnmt/early/2021/09/27/jnmt.121.262320.full.pdf"}],"tags":[],"related":["time-activity-curve","effective-half-life","becquerel-curie","o-15","rb-82"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","pet","spect"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics"},{"id":"dose-calibrator","kind":"term","name":"Dose calibrator","aka":[],"tldr":"A shielded instrument that measures exactly how much radioactivity is in a syringe or vial before it's given to a patient, so the dose matches the prescription.","summary":"A dose calibrator is a shielded, re-entrant ionisation chamber used to measure the activity (in becquerels or curies) of a radiopharmaceutical dosage before it is administered to a patient. Under US Nuclear Regulatory Commission rules, licensees performing direct dosage measurements must possess and use such instrumentation (10 CFR 35.60, formerly the more prescriptive 35.50), and calibrate it in accordance with nationally recognised standards or the manufacturer's instructions.\n\nUnder the earlier, more detailed version of the rule (still widely followed as practice standard and reflected in NRC guidance such as NUREG-1556 Vol. 9), dose calibrators must be checked for constancy each day of use with a dedicated check source of at least 10 microcuries of radium-226 or 50 microcuries of any other photon-emitting radionuclide; tested for accuracy on installation and at least annually by assaying two sealed sources of different radionuclides, each within 5% of its manufacturer-stated activity; tested for linearity on installation and at least quarterly across the full range of clinical use down to 10 microcuries; and tested for geometry dependence on installation across the range of volumes and containers used clinically. A dose calibrator must be repaired or replaced if its accuracy or constancy error exceeds 10%, and records of every check and test must be retained (historically for three years, per 10 CFR 35.2060).\n\nThe dose calibrator is the instrument that closes the loop between the pharmacy's compounding or dispensing step and the patient: the final patient dose or ordered amount must be radioassayed in it before administration (except for certain unopened manufacturer unit-dose containers), and the measured activity is decay-corrected to the scheduled administration time to confirm it falls within the prescribed and regulatory tolerance. It sits physically in the hot lab alongside survey instruments and syringe/vial shields.","asOf":"2026-09-22","links":[{"label":"10 CFR 35.60, Possession, use, and calibration of instruments used to measure the activity of unsealed byproduct material (Cornell LII)","url":"https://www.law.cornell.edu/cfr/text/10/35.60"},{"label":"NUREG-1556 Vol. 9: Consolidated Guidance About Materials Licenses (dose calibrator QC criteria)","url":"https://www.nrc.gov/docs/ML0228/ML022830849.pdf"},{"label":"Selected sections of 10 CFR Part 35, historical §35.50 dose calibrator requirements (NCBI Bookshelf)","url":"https://www.ncbi.nlm.nih.gov/books/NBK232708/"}],"tags":["NRC","quality control","instrumentation"],"related":["hot-lab","authorized-user","gamma-probes-dose-calibrators","release-criteria","radiopharmacy-term"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation"},{"id":"dosimetry","kind":"term","name":"Dosimetry","aka":[],"tldr":"Measuring how much radiation dose each organ and tumour actually received from a radioactive drug.","summary":"Dosimetry is the measurement of how much radiation dose each organ and each tumour actually received from a radioactive drug. It relies on post-therapy SPECT/CT imaging at several time points and enables personalised activity prescription instead of fixed doses, and regulators and payers increasingly require it. The term is linked to the SPECT & bone scan and Radioligand therapy (beta emitters) technologies and to Radioembolisation (TARE / SIRT, yttrium-90), Auger-electron therapy and Total-body PET for screening. It is referenced by the Hepatocellular carcinoma and Neuroendocrine tumours entries, the radiopharmaceutical roadmap and the bottleneck on wrong doses, and by ideas on dosimetry-personalised PRRT instead of four fixed cycles and total-body PET for personalised radioligand dosing.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Dosimetry","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Dosimetry"}],"tags":[],"related":["y-90"],"indications":[],"sections":[],"technologies":["spect","radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"effective-half-life","kind":"term","name":"Effective half-life","aka":[],"tldr":"The real-world time it takes for the radioactivity in a patient's organ to fall by half, combining both the radioactive atom's own decay and the body's own clearance of the drug. It is always shorter than either process acting alone, and it is the number that actually drives how much radiation dose an organ receives.","summary":"The effective half-life (Teff) is the time required for the radioactivity of a radiopharmaceutical within an organ or the whole body to fall to half its original value under the combined action of radioactive decay (physical half-life, Tphys) and biological elimination (biological half-life, Tbiol). Because both processes remove activity in parallel and independently, their rate constants add: 1/Teff = 1/Tphys + 1/Tbiol, equivalently Teff = (Tphys x Tbiol)/(Tphys + Tbiol); Teff is always shorter than whichever of Tphys or Tbiol is shorter, and it converges towards the shorter of the two when the two half-lives differ greatly (for a radionuclide with a very long physical half-life and fast biological clearance, Teff approaches Tbiol, and vice versa).\n\nEffective half-life is the quantity that actually appears in dosimetry calculations, because it describes how the true, measurable radioactivity in a source organ declines over time, which is exactly what a time-activity curve records and what must be integrated to obtain the time-integrated activity used in the MIRD formalism. It can be measured directly from serial quantitative imaging without needing to separately determine the physical and biological components.\n\nA practical example: 177Lu has a physical half-life of about 6.65 days; if a PSMA-targeted ligand clears from the kidneys with a biological half-life of a few days, the effective half-life in the kidney will be shorter than 6.65 days, meaning the kidney's radiation exposure is delivered, and finishes, faster than lutetium-177's own decay alone would suggest.","asOf":"2026-09-22","links":[{"label":"Wikipedia: effective half-life, derivation and formula","url":"https://en.wikipedia.org/wiki/Effective_half-life"},{"label":"Radiopharmacy teaching notes (Loyola University Chicago): effective, biological and physical half-life","url":"https://www.lumen.luc.edu/lumen/meded/radio/nuc_med/radpharm/sect-a3.htm"}],"tags":[],"related":["biological-half-life","half-life","time-activity-curve","decay-correction","lu-177"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","in-vivo-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics"},{"id":"equivalent-dose","kind":"term","name":"Equivalent dose and effective dose (sievert)","aka":[],"tldr":"A way of converting a physical radiation dose into a single number for comparing radiation risk across different types of radiation and different organs. It is used for radiation-protection purposes, not for prescribing cancer treatment doses.","summary":"Equivalent dose (H) adjusts the absorbed dose in an organ or tissue (measured in gray) by a radiation weighting factor (wR) that reflects how biologically damaging a given type of radiation is, compared with photons or beta particles of the same absorbed dose: H_T = sum over R of wR times D_T,R. Current ICRP values are wR = 1 for photons, electrons and beta particles, wR = 2 for protons, and wR = 20 for alpha particles, reflecting alpha particles' much higher biological potency per unit of physical dose. Equivalent dose is expressed in sievert (Sv), the same unit (J/kg) as gray but with a different name to signal that a biological weighting has been applied.\n\nEffective dose (E) goes one step further, multiplying the equivalent dose to each organ by a tissue weighting factor (wT, which sums to 1 across the whole body) that represents that organ's relative contribution to overall cancer and heritable-disease risk from uniform whole-body irradiation, then summing across organs. Effective dose, also in sievert, is the standard quantity used in radiation protection to compare the stochastic (cancer-risk) burden of different exposures, for example a diagnostic PET/CT scan versus natural background radiation.\n\nThese are protection quantities developed by the ICRP for population-level risk management and regulatory dose limits; they are not used to prescribe or evaluate radiopharmaceutical therapy, where the organ-specific absorbed dose in gray (via the MIRD formalism), sometimes adjusted for relative biological effectiveness rather than the fixed regulatory wR, is what guides treatment planning.","asOf":"2026-09-22","links":[{"label":"ICRP: The Use of Dosimetric Quantities in Radiological Protection","url":"https://www.icrp.org/docs/physics_icrp_found_doc_for_web_consult.pdf"},{"label":"ICRPaedia: Absorbed, Equivalent, and Effective Dose","url":"https://icrpaedia.org/Absorbed,_Equivalent,_and_Effective_Dose"}],"tags":[],"related":["absorbed-dose-term","relative-biological-effectiveness"],"indications":[],"sections":[],"technologies":["in-vivo-dosimetry","radioligand-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"dosimetry"},{"id":"estimand","kind":"term","name":"Estimands and intercurrent events (ICH E9(R1))","aka":["estimand","estimands","estimand framework","ICH E9(R1)","E9(R1)","intercurrent event","intercurrent events","treatment policy strategy","treatment policy estimand","hypothetical strategy","hypothetical estimand","composite strategy","while on treatment strategy","principal stratum","principal stratum strategy","sensitivity analysis","sensitivity analyses","missing data","missing data handling","handling of missing data","discontinued treatment","treatment discontinuation","rescue medication","subsequent anticancer therapy","what the trial is estimating"],"tldr":"An estimand is a precise statement of what question a trial is answering, including what to do about patients who switch treatment, stop early or start another drug; the ICH E9(R1) framework makes trials write this down before they start.","summary":"Two trials can measure the same endpoint and answer different questions. If a control patient crosses over to the experimental drug at progression, does the overall survival comparison ask what happens under the policy of assigning the drug (whatever patients later receive), or what would have happened had nobody crossed over? If a patient stops the drug for toxicity, is their later progression counted against the drug, or is the question about the effect while on treatment? These things that happen after randomisation and change what is measured are called intercurrent events, and the estimand framework in the 2019 addendum ICH E9(R1) requires a trial to name, for each one, the strategy it will use: treatment policy (count everything that happens, the classic intention-to-treat approach), hypothetical (estimate what would have happened without the event, as crossover adjustment does), composite (treat the event as part of the outcome), while-on-treatment, or principal stratum (restrict to the patients in whom the event would not occur under either arm).\n\nThe framework turns familiar arguments into explicit choices. The crossover debate over VISION and PSMAfore, where most control patients received the radioligand at progression, is a disagreement about estimands: the treatment policy estimand showed little overall survival difference, and the hypothetical estimand estimated by crossover-adjustment methods showed a larger one, and each answers a legitimate but different question. Intention-to-treat and per-protocol analyses in a non-inferiority trial such as PERSEPHONE are two estimands for the same data. Trials that add a new drug on top of a control that patients may later receive anyway, as in many adjuvant designs, are asking a treatment-policy question whether they say so or not.\n\nFor readers the practical use is a checklist: what population, what variable, what happens to the number when patients switch, stop or are lost, and what summary (a hazard ratio, a difference in proportions at a landmark) is reported. A trial that states its estimand in the protocol and reports sensitivity analyses under the alternatives is harder to spin than one that picks the most flattering analysis after the fact. Regulators now expect the estimand to be specified for the primary endpoint of every confirmatory trial.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Estimand","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Estimand"},{"label":"ICH E9 and E9(R1): statistical principles for clinical trials and the estimand framework","url":"https://www.ich.org/page/efficacy-guidelines"}],"tags":[],"related":["crossover"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["vision","psmafore"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Trials"},{"id":"fixed-versus-personalised-dosing","kind":"term","name":"Fixed versus personalised (dosimetry-guided) dosing","aka":[],"tldr":"Most radioactive cancer treatments today give every patient the same amount, on the same schedule, regardless of body size. Researchers are testing whether measuring how much radiation reaches a patient's kidneys and tumours, and adjusting the dose accordingly, works better and is safer.","summary":"Approved peptide receptor radionuclide therapy (lutetium-177 dotatate, Lutathera) and PSMA radioligand therapy (lutetium-177 vipivotide tetraxetan, Pluvicto) are both dosed as a fixed activity per cycle regardless of patient size: Lutathera as 7.4 GBq every 8 weeks for four cycles, the schedule used in NETTER-1, and Pluvicto similarly as a fixed per-cycle activity. This mirrors how most targeted small-molecule cancer drugs are dosed, but it ignores patient-to-patient variability in biodistribution, renal clearance and tumour burden, all of which change how much radiation different organs and tumours actually absorb from the same injected activity.\n\nDosimetry-guided (personalised) dosing instead measures absorbed dose to organs at risk (chiefly kidney and bone marrow) after each cycle, using post-therapy SPECT/CT or serial blood and imaging sampling, and adjusts the number of cycles or the activity of subsequent cycles to reach a pre-defined cumulative dose limit (commonly around 23 Gy to the kidney and roughly 2 Gy to bone marrow, thresholds extrapolated from external-beam radiotherapy experience). A single-centre Swedish phase 2 trial individualising the number of 177Lu-DOTATATE cycles by renal biological effective dose reported a 16% partial response rate, 66% stable disease, and a median progression-free survival of 29 months and overall survival of 47 months in 96 evaluable patients, comparable to or exceeding NETTER-1 in a similar population. The ongoing DUONEN phase 3 trial in Poland is comparing fixed 7.4 GBq dosing against several dosimetry-guided 177Lu/90Y regimens with per-cycle activity adjusted to organ dose.\n\nNo randomised trial has yet shown personalised dosing to be superior to the fixed NETTER-1/VISION schedules on a hard efficacy endpoint, and the nuclear medicine community has not agreed a single validated dosimetry methodology, which is why fixed dosing remains the regulatory-approved standard of care. The idea that dosimetry-personalised PRRT could replace four fixed cycles is an active research question rather than settled practice.","asOf":"2026-09-22","links":[{"label":"Sandström M, et al. Phase II trial: efficacy and safety of individualized, dosimetry-based 177Lu-DOTATATE (ILUMINET), Eur J Nucl Med Mol Imaging 2022","url":"https://link.springer.com/article/10.1007/s00259-022-05786-w"},{"label":"Haug AR. PRRT of neuroendocrine tumors: individualized dosimetry or fixed dose scheme? EJNMMI Res 2020","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7158965/"},{"label":"DUONEN trial: dosimetry-guided peptide receptor radionuclide therapy, Frontiers in Endocrinology 2025","url":"https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1716247/full"}],"tags":["dosimetry","PRRT","individualised therapy"],"related":["radioligand-dosimetry","prrt","itm-11","lutathera","pluvicto","idea-net-dosimetry-prrt","idea-total-body-pet-dosimetry","gray-unit","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"therapy"},{"id":"flare-phenomenon","kind":"term","name":"Flare phenomenon","aka":[],"tldr":"Right after some cancer treatments start working, a scan can briefly look worse before it looks better, because healing bone or an early immune response makes lesions light up more, not because the cancer has actually grown. Doctors wait and repeat the scan before deciding treatment has failed.","summary":"The flare phenomenon (bone flare or scintigraphic flare) is an apparent early worsening on a bone scan, PET or PSMA-PET scan that reflects a reparative or reactive process rather than true disease progression, and is followed by genuine improvement on later imaging if the underlying treatment is actually working. On technetium-99m bone scintigraphy it appears as new or more intense uptake at existing or previously inconspicuous lesions, driven by reparative osteoblastic mineralisation around healing metastases as bone lesions respond to hormone therapy, chemotherapy or bone-seeking radiopharmaceuticals; it typically appears between two weeks and three months after starting treatment, occasionally as late as six months. Reported incidence varies widely: series in patients starting first-line hormone therapy for metastatic prostate cancer describe flare in roughly 6-41% of patients depending on definition and timing of the repeat scan, and around 10% of patients receiving bone-seeking radiopharmaceutical therapy (strontium-89, samarium-153, rhenium-186, and radium-223) show a comparable flare pattern.\n\nBecause flare can be mistaken for progression, standard practice (reflected in the MD Anderson bone response criteria) is to continue therapy for a minimum of roughly 12 additional weeks before concluding a scan reflects true progression, and to confirm any apparent worsening with a repeat scan 2-3 months later showing subsequent improvement, rather than acting on a single early scan. A parallel phenomenon, PSA flare (a transient early rise in prostate-specific antigen after starting androgen deprivation therapy or antiandrogens, from an initial agonist effect before suppression takes hold), is a distinct biochemical marker that does not always occur together with bone flare; in one series both bone and PSA flare co-occurred in only about one in four patients showing either.\n\nOn PSMA-PET, flare has been studied less consistently: one cohort study found no clear PSMA expression flare after starting androgen-receptor-pathway inhibitors, while retaining the possibility that a short-duration or very early flare could have been missed, so PSMA-PET response assessment guidance generally still recommends confirmatory follow-up imaging before calling early progression, particularly close to treatment initiation.","asOf":"2026-09-22","links":[{"label":"Conteduca V, et al. Flare phenomenon in prostate cancer: recent evidence on new drugs and next generation imaging, Ther Adv Med Oncol 2021","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7907710/"},{"label":"Radiopaedia: Flare phenomenon (bone scintigraphy)","url":"https://radiopaedia.org/articles/flare-phenomenon-bone-scintigraphy?lang=us"},{"label":"Flare phenomenon visualized by 99mTc-bone scintigraphy has favourable prognostic value in mCRPC, Ann Nucl Med 2024","url":"https://link.springer.com/article/10.1007/s12149-024-01914-8"}],"tags":["response assessment","bone imaging","prostate cancer"],"related":["bone-metastases","psa-kinetics","prostate-mcrpc","psma-pet","radium-223","complete-response-term","tc-99m","ra-223","sm-153","sr-89"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"imaging"},{"id":"gray-unit","kind":"term","name":"Gray unit (Gy)","aka":["cGy","centigray","EQD2","BED","biologically effective dose","dose escalation","dose-escalated","radiation dose","absorbed dose","prescribed dose","total dose","60 Gy","70 Gy","GBq","MBq","becquerel"],"tldr":"The unit of radiation dose absorbed by tissue: one gray is one joule per kilogram. A curative course is typically 50-70 Gy in total; a single bone-pain treatment is 8 Gy. Radiopharmaceuticals are prescribed by activity in becquerels (GBq) instead.","summary":"Because biological effect depends on both total dose and dose per fraction, different schedules are compared with the equivalent dose in 2 Gy fractions (EQD2) or biologically effective dose (BED); cervical brachytherapy aims for ≥85 Gy EQD2, early lung SBRT for BED ≥100 Gy. Dose escalation beyond 60 Gy did not help in stage III lung cancer (RTOG 0617) but did in prostate cancer. For radioligand therapy the administered activity (7.4 GBq of 177Lu-PSMA-617) is fixed, and dosimetry estimates the resulting gray to tumour and kidneys. Whole-body doses above about 4 Gy are lethal without marrow rescue, which is the basis of total body irradiation conditioning.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Gray_(unit)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Gray_(unit)"}],"tags":[],"related":["dosimetry","lu-177"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"half-life","kind":"term","name":"Half-life","aka":["half-lives","half life","plasma half-life","elimination half-life","pharmacokinetics","pharmacokinetic","PK","cleared from the body","drug exposure","peak concentration","Cmax","AUC","steady state","steady-state"],"tldr":"The time it takes for the amount of a drug in the blood to fall by half. It sets how often a drug must be given: hours to a day for small molecules such as kinase inhibitors, so they are taken daily, and two to four weeks for antibodies, so they are given every three or six weeks.","summary":"Small molecules are typically cleared by the liver and kidneys within hours to a day, so kinase inhibitors are taken daily; antibodies are protected from breakdown by recycling receptors and persist for two to four weeks, allowing dosing every three or six weeks. Half-life shapes both benefit and harm: a long-lived checkpoint inhibitor keeps working, and keeps causing immune side effects, for months after the last dose, while a radioactive drug's physical half-life (6.6 days for lutetium-177, 10 days for actinium-225) determines how long it irradiates the tumour. Pharmacokinetics is the study of these processes, and matching dose and schedule to them is central to dose optimisation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Biological_half-life","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Biological_half-life"}],"tags":[],"related":["alpha-vs-beta","dosimetry","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"hot-lab","kind":"term","name":"Hot lab (radiopharmacy dispensing area)","aka":[],"tldr":"The specially shielded room in a hospital or radiopharmacy where radioactive drugs are received, checked, prepared and measured before they are given to patients.","summary":"A hot lab is the shielded workspace within a nuclear medicine department or radiopharmacy where unsealed radioactive materials are received, surveyed, assayed, compounded or drawn into unit doses, and staged for use or decay-in-storage disposal. It typically houses a dose calibrator (a shielded re-entrant ionisation chamber used to assay every dose before administration), an L-block workstation with leaded glass shielding, syringe and vial shields of lead or tungsten, a fume hood or laminar-flow cabinet for volatile or aseptic compounding, generator storage (for example Mo-99/Tc-99m generators), a decay-in-storage area for short-lived waste, and contamination survey and monitoring equipment. \"Hot cell\" refers more specifically to a heavily shielded enclosure, often with remote manipulators and lead-glass viewing windows, used to handle the highest-activity materials, such as commercial radiopharmaceutical production or generator processing, without direct manual contact.\n\nBecause the hot lab concentrates the highest activities handled anywhere in a facility, its physical design (shielding thickness, room layout, ventilation and workflow zoning) is calculated by a qualified expert, typically a board-certified medical physicist, based on the isotopes used, weekly workload, occupancy of adjacent areas, and distance to occupied space, with the design goal of keeping public exposure below the 10 CFR 20.1301 limits (2 mrem in any one hour, 100 mrem per year) and occupational exposure within ALARA. Regulatory requirements for the hot lab's instruments and procedures flow from 10 CFR Part 35 (dose calibrators under 35.60/35.63, survey instruments under 35.61, labelling of vials and syringes under 35.69, and daily/weekly area surveys under 35.70).\n\nThe hot lab is where most of the practical burden of radiopharmaceutical GMP and release sits: incoming shipment surveys, generator eluate testing for radionuclidic breakthrough, on-site kit preparation and quality control (radiochemical purity, pH, sterility as applicable under USP <825>), and the final dose-calibrator assay that confirms the activity to be given to each patient matches the prescription.","asOf":"2026-09-22","links":[{"label":"Wikipedia: Hot cell","url":"https://en.wikipedia.org/wiki/Hot_cell"},{"label":"10 CFR Part 35, Subpart C - General Technical Requirements (dose calibrators, surveys, labelling)","url":"https://www.law.cornell.edu/cfr/text/10/part-35/subpart-C"},{"label":"10 CFR 20.1301, Dose limits for individual members of the public (NRC eCFR)","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-20/subpart-D/section-20.1301"}],"tags":["radiopharmacy","shielding","facility design"],"related":["dose-calibrator","radiopharmacy-term","alara","radiation-safety-officer","release-criteria","radionuclide-generators-kits","sterile-fill-finish","tc-99m","mo-99"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation"},{"id":"krenning-score","kind":"term","name":"Krenning score","aka":[],"tldr":"A 0-to-4 scale doctors use to describe how strongly a tumour lights up on a somatostatin receptor scan, by comparing it with the normal liver and spleen. A higher score generally means the tumour is a good candidate for peptide receptor radionuclide therapy.","summary":"The Krenning score is a five-point visual grading system (0-4) developed for planar and SPECT imaging with 111In-pentetreotide (OctreoScan), which grades tumour uptake of a somatostatin receptor tracer against two internal reference tissues: normal liver (grades 1-3) and spleen or kidney (grade 4). Grade 0 is no uptake; grade 1 is uptake below liver; grade 2 is uptake equal to or slightly less than liver; grade 3 is uptake greater than liver; grade 4 is uptake greater than spleen or kidney. The NETTER-1 trial required tumour uptake at least equal to normal liver (Krenning grade 2 or above) for enrolment, and a score greater than 2 is the practical threshold most centres use when selecting patients for PRRT with lutetium-177 dotatate.\n\nThe score has been extrapolated to gallium-68 and copper-64 DOTATATE PET/CT as a \"modified Krenning score\", but the correlation between the original scintigraphy-derived score and the PET-derived score is limited: PET is more sensitive, is acquired around one hour after injection rather than 24 hours, and tends to grade the same lesion higher. For lesions larger than 2 cm the modified score is considered more reliable; centres should state which imaging method and which reference organ underlie a reported grade.\n\nThe score is lesion-level and visual rather than quantitative, so heterogeneous disease (some lesions with low uptake alongside others with high uptake) requires reporting each discordant lesion separately rather than a single summary number, since a single index-lesion grade can misrepresent overall receptor status across the body.","asOf":"2026-09-22","links":[{"label":"Radiopaedia: Krenning score of neuroendocrine tumour uptake","url":"https://radiopaedia.org/articles/krenning-score-of-neuroendocrine-tumour-uptake?lang=us"},{"label":"Somatostatin receptor imaging and theranostics: current practice and future prospects (JNM/PMC, 2021)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9364764/"}],"tags":["scoring system","SSTR imaging","PRRT eligibility"],"related":["ga68-dotatate","sstr-pet","prrt","itm-11","lutathera","neuroendocrine","netter-1","ga-68","in-111","cu-64","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"imaging"},{"id":"ligand","kind":"term","name":"Ligand","aka":["ligands","binding partner"],"tldr":"The molecule that fits into a receptor and switches it on: growth factors, hormones and cytokines are all ligands. Cancers make their own ligands or mutate receptors so none is needed, and some drugs act on the ligand itself, as bevacizumab does by soaking up VEGF.","summary":"Ligand binding changes the receptor's shape and starts a signal inside the cell; the specificity of the fit is why one growth factor activates one family of receptors. Cancers exploit ligands by making their own (autocrine signalling), by persuading neighbouring cells to make them, or by mutating receptors so they no longer need the ligand at all. Several drugs act on ligands rather than receptors: bevacizumab soaks up VEGF before it can reach its receptor, and 'radioligands' are small molecules or peptides that bind a receptor such as PSMA to deliver radiation.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Ligand_(biochemistry)","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Ligand_(biochemistry)"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":["psma"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"linear-energy-transfer","kind":"term","name":"Linear energy transfer (LET)","aka":[],"tldr":"A measure of how densely a particle of radiation deposits its energy as it travels through tissue. Alpha particles dump their energy in a short, dense burst; beta particles and gamma rays spread it thinly over a much longer track.","summary":"Linear energy transfer (L or LET) is the average energy that a charged ionising particle transfers to the medium per unit length of its track, L = dE/dl, expressed in keV per micrometre (keV/µm). It describes the spatial density of energy deposition (and therefore of ionisation events) along a particle's path, which is what ultimately determines the biological severity of the damage caused for a given absorbed dose.\n\nRepresentative values illustrate the range: cobalt-60 gamma rays and diagnostic x-rays are low-LET (roughly 0.2-2 keV/µm), beta particles from radionuclides such as lutetium-177 are also low-LET (a 1 MeV beta particle deposits roughly 0.2 keV/µm and travels several millimetres), while alpha particles are high-LET, depositing on the order of 80-150 keV/µm over a track of only tens to about a hundred micrometres (a handful of cell diameters). High-LET radiation causes densely clustered ionisations that produce more complex, harder-to-repair DNA double-strand breaks than the sparse ionisation from low-LET beta or gamma radiation, which is the physical basis for targeted alpha therapy's distinct toxicity and efficacy profile compared with beta-emitting radioligand therapy.\n\nLET is the mechanistic quantity underlying both the regulatory radiation weighting factor used in equivalent dose (wR = 20 for alpha versus 1 for beta/gamma) and the empirically measured relative biological effectiveness used to compare therapeutic effect between alpha- and beta-emitting radiopharmaceuticals.","asOf":"2026-09-22","links":[{"label":"NRC training materials: interaction of charged particles with matter, LET and stopping power","url":"https://www.nrc.gov/docs/ml1122/ml11229a666.pdf"},{"label":"ScienceDirect Topics: linear energy transfer, representative values","url":"https://www.sciencedirect.com/topics/immunology-and-microbiology/linear-energy-transfer"}],"tags":[],"related":["relative-biological-effectiveness","equivalent-dose","alpha-vs-beta","lu-177"],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy","auger-electron-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics"},{"id":"mcrpc-mhspc","kind":"term","name":"mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)","aka":["castration-resistant","castration resistant","castrate-resistant","mCRPC","nmCRPC","CRPC","castration-sensitive","castration sensitive","hormone-sensitive","hormone sensitive","mHSPC","mCSPC","HSPC","hormone-naive","hormone-refractory","biochemical recurrence","PSA recurrence","rising PSA","PSA progression","rPFS"],"tldr":"Prostate cancer starts out fed by testosterone (hormone-sensitive) and shrinks when it is removed. When it learns to grow despite castrate testosterone levels it is called castration-resistant, a later and more dangerous stage with its own treatments.","summary":"Metastatic hormone-sensitive disease (mHSPC) is treated with androgen deprivation plus an ARPI (abiraterone, enzalutamide, apalutamide, darolutamide) and sometimes docetaxel (STAMPEDE, LATITUDE, ARASENS), which delays castration resistance by years. Castration-resistant disease (CRPC), defined by PSA or radiographic progression with testosterone <50 ng/dL, arises through androgen receptor amplification, mutations, splice variants (AR-V7) and intratumoural androgen synthesis; it is treated with ARPI switch, docetaxel and cabazitaxel, PARP inhibitors for HRR mutations, 177Lu-PSMA-617 (VISION, PSMAfore) and radium-223. Non-metastatic CRPC (rising PSA, clear scans) has its own approvals. Radiographic PFS (rPFS) is the usual endpoint.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Prostate_cancer#Castration-resistant_prostate_cancer","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prostate_cancer#Castration-resistant_prostate_cancer"}],"tags":[],"related":["arpi","lu-177","ra-223"],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":["abiraterone","enzalutamide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["stampede","vision","psmafore"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"medicare-ced","kind":"term","name":"Medicare coverage with evidence development","aka":["coverage with evidence development","CED","national coverage determination","national coverage determinations","NCD 90.2","Medicare NGS coverage","Medicare coverage of cancer drugs","protected classes"],"tldr":"Medicare's way of paying for a promising but uncertain test or treatment only for patients enrolled in a registry or study, used for PET scans in cancer from 2006 and now the frame for how Medicare covers gene panels and cell therapies.","summary":"United States, agency guidance under the Social Security Act. Coverage with evidence development (CED) lets the Centers for Medicare and Medicaid Services issue a national coverage determination that pays for an item only when the patient is in an approved study or registry, under section 1862(a)(1)(E) of the Social Security Act. CMS set out the policy in 2006 guidance, revised in 2014 and again in 2024. Primary text: the CMS CED page and the Medicare Coverage Database.\n\nOncology examples: FDG-PET for most cancers was covered from 2006 through the National Oncologic PET Registry, which then generated the evidence that led to unrestricted coverage in 2009 and 2013. National coverage determination 90.2 (March 2018, widened in 2020) covers FDA-approved next-generation sequencing companion diagnostics for patients with advanced cancer, and germline testing for hereditary cancer. CAR-T therapy received a national coverage determination in August 2019 after an initial proposal to impose CED was dropped. More broadly, Medicare Part B must cover anti-cancer drugs for uses supported by the statutory compendia, and Part D treats antineoplastics as a protected class, so unlike Europe there is no national decision on whether a cancer drug is worth its price.\n\nThe arguments: CED is praised for turning coverage into evidence and criticised for slow registries that never end; the compendia rule and protected classes are why the United States pays for nearly every approved cancer drug at list price, which the Inflation Reduction Act's negotiation programme begins to change.","asOf":"2026-09-17","links":[{"label":"CMS: coverage with evidence development","url":"https://www.cms.gov/medicare/coverage/evidence"},{"label":"CMS: Medicare Coverage Database","url":"https://www.cms.gov/medicare-coverage-database/"}],"tags":["law","us"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Regulation & policy"},{"id":"curie-siopen-score","kind":"term","name":"MIBG Curie and SIOPEN scores","aka":["Curie score","SIOPEN score","MIBG score","MIBG avidity","MIBG-avid","MIBG-non-avid","semi-quantitative MIBG scoring","123I-MIBG scan","MIBG scintigraphy","18F-MFBG PET","MFBG PET"],"tldr":"Neuroblastoma soaks up MIBG, a radioactive cousin of noradrenaline; the Curie and SIOPEN scores count how many body regions still light up on the scan, and a score that has not fallen enough after the first rounds of chemotherapy marks a child who is unlikely to be cured with the standard plan.","summary":"What is measured: the extent of MIBG-avid disease on a whole-body scan. How: iodine-123 MIBG planar and SPECT imaging (with a bone scan or FDG PET for the roughly 10 percent of tumours that do not take up MIBG); the Curie score grades nine skeletal segments and one soft-tissue site from 0 to 3 (maximum 30) and the SIOPEN score grades twelve skeletal segments from 0 to 6 (maximum 72). What a result changes: at diagnosis it stages metastatic disease and establishes MIBG avidity for later iodine-131 MIBG therapy; after induction, a Curie score above 2 (COG A3973) or a SIOPEN score above 3 predicts worse event-free survival in high-risk disease and is used to stratify and to select patients for intensified or experimental arms, such as adding iodine-131 MIBG in COG ANBL1531; the International Neuroblastoma Response Criteria of 2017 use MIBG to score skeletal response. Fluorine-18 MFBG PET, a same-day tracer with higher resolution, is replacing MIBG in trials. Where it matters: neuroblastoma and high-risk neuroblastoma.","asOf":"2026-09-17","links":[],"tags":[],"related":["mibg-theranostics","i131-mibg","fdg-pet","f-18","i-123","i-131"],"indications":["neuroblastoma","neuroblastoma-high-risk"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"mird-formalism","kind":"term","name":"MIRD formalism","aka":[],"tldr":"The standard recipe physicists use to work out how much radiation dose a patient's organs and tumours actually received from an injected radioactive drug, based on how long it stayed in the body and where it went.","summary":"The Medical Internal Radiation Dose (MIRD) formalism, developed by the MIRD Committee of the Society of Nuclear Medicine and Molecular Imaging, is the standard framework for calculating the absorbed dose to a target region of the body from a radionuclide distributed in one or more source regions. In its simplified organ-level form, the mean absorbed dose to a target region equals the time-integrated activity in a source region multiplied by an 'S value': D = A-tilde x S, where the S value (units of Gy per Bq-s, or a convenient multiple) is a radionuclide- and geometry-specific constant representing the absorbed dose rate per unit activity, computed from the energies and yields of all emitted radiations and the fraction of that energy absorbed in the target given the source-target anatomy (the absorbed fraction).\n\nThe other half of the calculation is the time-integrated activity (historically called cumulated activity), obtained by integrating the time-activity curve, the measured activity in a source region plotted against time after injection, over the treatment or imaging period; dividing by the administered activity gives the time-integrated activity coefficient (formerly 'residence time'). S values have been tabulated for many radionuclides and source-target organ pairs using standardised anthropomorphic reference phantoms (MIRD Pamphlets 11 and 21, and successor tools such as MIRDcalc), and voxel-level S values extend the same schema to patient-specific 3D dosimetry from SPECT/CT or PET/CT.\n\nThe MIRD schema underpins essentially all clinical and research dosimetry for radioligand therapy, including personalised activity prescription, and it is functionally similar to (and cross-validated against) the ICRP's own internal dosimetry system, both built on the same underlying physics of time-integrated activity and absorbed fraction.","asOf":"2026-09-22","links":[{"label":"Journal of Nuclear Medicine: MIRD Pamphlet No. 21, a generalized schema for radiopharmaceutical dosimetry","url":"https://jnm.snmjournals.org/content/50/3/477"},{"label":"Journal of Nuclear Medicine Technology: the MIRD schema for radiopharmaceutical dosimetry, a review","url":"https://tech.snmjournals.org/content/jnmt/52/2/74.full.pdf"}],"tags":[],"related":["absorbed-dose-term","time-activity-curve","activity-prescription"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","in-vivo-dosimetry","lu177-radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"dosimetry"},{"id":"myelosuppression-after-rlt","kind":"term","name":"Myelosuppression after radioligand therapy","aka":[],"tldr":"Radioactive cancer treatments that circulate through the blood also irradiate bone marrow, so blood counts (red cells, white cells, platelets) can drop. Doctors check blood counts regularly and pause or reduce treatment if counts fall too far.","summary":"Because radioligand therapies circulate systemically before binding their target, bone marrow receives incidental irradiation and can develop dose-related cytopenias. In the VISION trial of lutetium-177 vipivotide tetraxetan (Pluvicto) for metastatic castration-resistant prostate cancer, grade 3-4 laboratory abnormalities occurred in 15% of patients for decreased haemoglobin, 9% for decreased platelets, 7% for decreased leukocytes and 4.5% for decreased neutrophils; grade 3-4 pancytopenia occurred in 1.1% including two fatal events, and four myelosuppression-related deaths were reported in total (from intracranial or subdural haemorrhage associated with thrombocytopenia, sepsis with neutropenia, and bone marrow failure). In the earlier-line PSMAfore and PSMAddition trials, grade 3-4 rates were generally lower (for example, grade 3-4 decreased haemoglobin 7% and 4.3% respectively), consistent with less marrow reserve in more heavily pretreated VISION-era patients.\n\nThe Pluvicto label requires complete blood counts before and during treatment and specifies dose modifications for myelosuppression: withhold for grade 2, and withhold plus reduce the dose by 20% (to 5.9 GBq/160 mCi) for grade 3 or higher, with permanent discontinuation for recurrent grade 3 or higher myelosuppression after one dose reduction. Lymphopenia is the most frequent laboratory abnormality overall, reported in over 80-90% of patients at any grade in pooled analyses, reflecting the radiosensitivity of lymphocytes.\n\nFor peptide receptor radionuclide therapy with lutetium-177 dotatate, grade 3-4 haematological toxicity is less frequent, reported around 9-13% in cohort series, generally reversible, and less common than with the historical 90Y-labelled somatostatin analogues. Risk factors for more severe myelosuppression across radioligand therapies include extensive bone marrow involvement by tumour, prior chemotherapy or external beam radiotherapy, and impaired baseline renal function, since slower renal clearance prolongs the radiopharmaceutical's circulation time and marrow exposure.","asOf":"2026-09-22","links":[{"label":"FDA label: Pluvicto, dosage modifications and adverse reactions","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215833s021s024lbl.pdf"},{"label":"Novartis Pluvicto prescribing information (Warnings and Precautions: myelosuppression)","url":"https://www.novartis.com/us-en/sites/novartis_us/files/pluvicto.pdf"},{"label":"Efficacy and Toxicity of [177Lu]Lu-PSMA-617 for Metastatic CRPC (expanded access programme vs VISION), J Nucl Med 2024","url":"https://jnm.snmjournals.org/content/65/11/1740"}],"tags":["adverse effect","haematology","radioligand therapy"],"related":["pluvicto","vision","psmafore","cytopenias","thrombocytopenia","anaemia","bone-marrow","prrt","lutathera","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"safety"},{"id":"net-grade-ki67","kind":"term","name":"Neuroendocrine tumour grade (Ki-67) and WHO classification","aka":[],"tldr":"How fast the tumour cells are dividing, measured by Ki-67 staining, separates slow-growing neuroendocrine tumours from aggressive neuroendocrine carcinomas and decides the treatment.","summary":"WHO 2019/2022: well-differentiated NET grade 1 (Ki-67 <3%), grade 2 (3-20%), grade 3 (>20%, well-differentiated); poorly differentiated neuroendocrine carcinoma (NEC, small- or large-cell) is a separate lineage treated like small-cell lung cancer. Grade drives choice among somatostatin analogues, PRRT, targeted therapy and chemotherapy.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Neuroendocrine_tumor"}],"tags":[],"related":[],"indications":["neuroendocrine","sclc","grade-3-net"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Pathology"},{"id":"no-carrier-added","kind":"term","name":"No-carrier-added (n.c.a.) and carrier-added production","aka":[],"tldr":"A way of describing how 'pure' a batch of radioactive material is: whether ordinary, non-radioactive atoms of the same element were deliberately or accidentally mixed in during manufacture.","summary":"'No-carrier-added' (n.c.a.) describes a radionuclide preparation in which no stable (non-radioactive) isotope of the same element has been intentionally added during manufacture or processing, though trace stable-isotope contamination can still occur incidentally, for example from reagents, the target material or the separation chemistry. 'Carrier-added' means stable isotope was deliberately added, usually to help a separation or purification step proceed. 'Carrier-free' is a stricter, largely theoretical state in which no stable isotope of the element is present at all; it is essentially never achieved or independently proven in practice for radiometals used in radiopharmaceuticals, and most style guides advise against using the term unless analytically verified.\n\nThe distinction matters most for reactor-produced radiometals. Lutetium-177 made by direct neutron irradiation of enriched 176Lu (176Lu(n,γ)177Lu) is carrier-added, because it comes out mixed with a large excess of unreacted, non-radioactive 176Lu in the same chemical form, which cannot be separated from 177Lu by ordinary chemistry since they are the same element. The alternative route, irradiating 176Yb to make 177Yb, which decays to 177Lu, gives no-carrier-added lutetium-177, because ytterbium and lutetium are different elements and can be chemically separated, leaving a batch with much higher specific activity.\n\nThese qualitative labels are convenient shorthand but are not a substitute for a measured specific or molar activity value, which is what a quality-control release specification and a clinical protocol actually need.","asOf":"2026-09-22","links":[{"label":"IAEA TECDOC: specific activity determination and no-carrier-added definition","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/TE-1856web.pdf"},{"label":"IAEA: cyclotron produced radionuclides, principles and practice","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/trs465_web.pdf"}],"tags":[],"related":["specific-activity","lu-177"],"indications":[],"sections":[],"technologies":["research-reactor-isotope-production","therapy-isotope-supply-chain"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"chemistry"},{"id":"nrc-licensing","kind":"term","name":"NRC medical-use licensing (10 CFR Part 35)","aka":[],"tldr":"Any US clinic that wants to use radioactive drugs for patients must first get a specific license, either from the federal Nuclear Regulatory Commission or from the state government where it's located, proving it can handle the material safely.","summary":"In the United States, a person or institution may manufacture, produce, acquire, receive, possess, prepare, use or transfer byproduct material for medical use only under a specific license issued by the Nuclear Regulatory Commission (NRC) or by an Agreement State, under 10 CFR Part 35, \"Medical Use of Byproduct Material.\" Part 35 divides medical use into distinct categories with their own subparts: uptake, dilution and excretion studies not requiring a written directive (35.100); imaging and localisation studies not requiring a written directive, i.e. most diagnostic PET and SPECT tracers (35.200); uses requiring a written directive, i.e. most therapeutic radiopharmaceuticals (35.300); manual brachytherapy (35.400); sealed sources for diagnostic use (35.500); sealed sources in remote afterloaders, teletherapy and gamma stereotactic units (35.600); and any other medical use not specifically addressed elsewhere (35.1000).\n\nAgreement States are US states that have entered into an agreement with the NRC under section 274b of the Atomic Energy Act, giving the state authority to license and inspect byproduct, source, and certain special nuclear materials within its borders; the large majority of US states are Agreement States, so most medical-use licenses are issued and inspected by state radiation control programmes rather than the NRC directly, applying regulations that must be compatible with, though not always textually identical to, Part 35. Non-Agreement States and federal enclaves remain under direct NRC jurisdiction.\n\nThe NRC issues two broad types of specific license for medical use: a specific license of limited scope, tailored to the particular radionuclides, forms and medical uses named on the license, and a specific license of broad scope (issued under 10 CFR Part 33), which authorises a wider range of quantities and uses, typically for large academic medical centres, and carries additional internal radiation safety committee obligations in exchange for more flexibility. An applicant applies using NRC Form 313, must demonstrate through named, individually qualified staff (Authorized Users, Radiation Safety Officer, Authorized Medical Physicists, Authorized Nuclear Pharmacists as applicable) that it is equipped and committed to meet Part 35's safety standards, and must amend its license before adding new radionuclides, new uses, or new addresses of use.","asOf":"2026-09-22","links":[{"label":"eCFR: 10 CFR Part 35, Medical Use of Byproduct Material - full text and subpart structure","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35"},{"label":"NUREG-1556 Vol. 9: Consolidated Guidance About Materials Licenses for medical use, licensing overview and Agreement States","url":"https://www.nrc.gov/docs/ML1632/ML16328A214.pdf"},{"label":"NRC: Frequently Asked Questions About Licensing Medical Uses of Byproduct Material","url":"https://www.nrc.gov/materials/miau/med-use-toolkit/faqs-part35"}],"tags":["NRC","10 CFR Part 35","Agreement States"],"related":["authorized-user","radiation-safety-officer","hot-lab","alara","patient-release-criteria","dose-calibrator"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation"},{"id":"oligometastatic","kind":"term","name":"Oligometastatic disease","aka":[],"tldr":"Cancer that has spread to only a few places, which may still be curable by treating each spot.","summary":"Oligometastatic disease is cancer that has spread to only a few sites, usually no more than three to five metastases, and may still be curable if each spot is treated. The SABR-COMET trial supported metastasis-directed SBRT / SABR (stereotactic radiotherapy), and the ESTRO/EORTC classification distinguishes synchronous, oligorecurrent and oligoprogressive disease, the last covered by the related term Oligoprogression. PSMA PET has expanded detection of this state in Prostate cancer, and the term is also referenced by the Renal cell carcinoma entry and the bottleneck on metastasis biology. Ideas building on it include PSMA-PET-guided metastasis-directed therapy as a curative strategy and a test to tell true oligometastatic disease from hidden widespread spread.","asOf":"2026-09-04","links":[{"label":"NCI Dictionary of Cancer Terms: oligometastasis","url":"https://www.cancer.gov/publications/dictionaries/cancer-terms/def/oligometastasis"},{"label":"Lievens et al., Defining oligometastatic disease from a radiation oncology perspective: an ESTRO-ASTRO consensus (Radiotherapy and Oncology 2020)","url":"https://doi.org/10.1016/j.radonc.2020.04.003"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinical"},{"id":"partial-volume-effect","kind":"term","name":"Partial volume effect (PVE)","aka":[],"tldr":"A PET or SPECT scan can make small tumours or lesions look fainter than they really are, simply because the scanner cannot see fine detail perfectly; the true 'brightness' gets smeared out over a wider area, especially in objects smaller than about 1-2 cm.","summary":"The partial volume effect is the systematic underestimation of measured activity concentration in objects that are small relative to the spatial resolution of a PET or SPECT imaging system, caused by two combined phenomena: the finite spatial resolution of the scanner blurs the true activity distribution (a 3D convolution with the system's point-spread function), causing signal to 'spill out' of small hot lesions and background signal to 'spill in'; and the sampling of a continuous activity distribution onto a discrete voxel grid means boundary voxels contain a mixture of tissues (the tissue-fraction effect). Both effects become significant when an object's smallest dimension is below roughly two to three times the system's full-width-at-half-maximum (FWHM) spatial resolution, corresponding to roughly 6-15 mm for typical PET systems and roughly 14-25 mm for SPECT systems, which have poorer intrinsic resolution.\n\nThe practical consequence is a size-dependent, reproducible bias, not random noise: the smaller the lesion, the greater the underestimation of measured uptake (SUVmax or SUVmean) or, for post-therapy dosimetry, of the true absorbed dose. In one worked clinical example, SPECT-based lesion dosimetry for 177Lu therapy underestimated the true absorbed dose by more than 60% in a roughly 1 cm lesion and by more than 99% in a lesion only a few millimetres across.\n\nPartial volume effect matters for radiopharmaceutical therapy dosimetry because small metastases, exactly the lesions most likely to be missed or under-dosed, are the ones most affected; it also affects diagnostic PET quantification, where small lymph nodes below about 10 mm read out with substantially lower SUV than their true uptake. Partial volume correction methods (recovery-coefficient-based, MRI- or CT-guided) can partly compensate but rarely restore full accuracy for sub-centimetre structures, and current guidance recommends excluding lesions below about 10 mm from quantitative analysis unless a validated correction method is applied.","asOf":"2026-09-22","links":[{"label":"PMC: partial volume effect in SPECT and PET imaging and impact on dosimetry","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9803618/"},{"label":"Journal of Nuclear Medicine: partial-volume effect in PET tumor imaging","url":"https://jnm.snmjournals.org/content/48/6/932"}],"tags":[],"related":["attenuation-correction","suv","time-of-flight-pet","lu-177"],"indications":[],"sections":[],"technologies":["pet","spect","quantitative-imaging-biomarkers","radioligand-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics"},{"id":"patient-release-criteria","kind":"term","name":"Patient release criteria after radioactive treatment","aka":[],"tldr":"After certain radioactive treatments, US rules set a specific radiation limit that must be checked before a patient can safely go home, and if the dose to a household member could exceed a lower limit, the patient gets written safety instructions (including, if relevant, guidance on breastfeeding).","summary":"Under 10 CFR 35.75, a US licensee may authorise the release from control of a patient (or a patient carrying an implant) containing unsealed byproduct material or brachytherapy sources if the total effective dose equivalent (TEDE) to any other individual from exposure to the released patient is not likely to exceed 5 mSv (0.5 rem). This single numeric threshold, rather than a fixed activity limit for each radionuclide, is what actually governs same-day release after therapies such as iodine-131 for thyroid cancer, lutetium-177 radioligand therapy, or brachytherapy implants, and licensees typically use NRC-provided tables of activities, dose-rate measurements, or patient-specific calculations to demonstrate compliance before discharge.\n\nA second, lower threshold triggers a documentation and counselling obligation rather than a release bar: if the TEDE to any other individual is likely to exceed 1 mSv (0.1 rem), the released individual (or their parent or guardian) must be given written instructions on actions to keep the dose to others as low as reasonably achievable. If a nursing infant or child could receive more than 1 mSv assuming breastfeeding continues uninterrupted, those instructions must also cover guidance on interrupting or discontinuing breastfeeding and the potential consequences of not following that guidance. The licensee must keep a record of the basis for authorising release and, separately, a record of any instructions given to a breastfeeding patient (10 CFR 35.2075).\n\nThese thresholds are considerably more permissive than the general public dose limit (1 mSv/year total, under 10 CFR Part 20), reflecting a deliberate policy choice that patients undergoing medically necessary radioactive treatment, and the household members who choose to live with them, accept a higher, time-limited exposure than an uninvolved member of the public would. Facilities commonly apply extra margin above the regulatory minimum (for example, discharging only once a fixed dose-rate-at-one-metre threshold is met) and provide take-home instructions covering distance, time and hygiene precautions for a defined number of days, tailored to the isotope's half-life and the specific therapy given. This entry reflects the regulation as published in the eCFR, checked 2026-09-22; consult the current eCFR text for any amendments.","asOf":"2026-09-22","links":[{"label":"eCFR: 10 CFR 35.75, Release of individuals containing unsealed byproduct material or implants containing byproduct material","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35/subpart-D/section-35.75"},{"label":"eCFR: 10 CFR Part 35, Medical Use of Byproduct Material (subpart structure, 35.2075 recordkeeping)","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35"}],"tags":["NRC","10 CFR 35.75","patient discharge"],"related":["nrc-licensing","authorized-user","radiation-safety-officer","radioiodine-therapy","lutathera","pluvicto","alara","lu-177","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation"},{"id":"payload","kind":"term","name":"Payload (ADC)","aka":[],"tldr":"The payload is the poison an ADC carries, usually a chemotherapy far too toxic to give on its own.","summary":"The payload is the cytotoxic warhead conjugated to the antibody. Classes: tubulin inhibitors (MMAE, MMAF, DM1, DM4), topoisomerase-I inhibitors (DXd, SN-38, exatecan, belotecan derivatives), DNA-damaging agents (PBD dimers, calicheamicin, duocarmycin). Newer payloads: degraders, immune agonists, radionuclides. Membrane permeability determines bystander killing.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Antibody-drug_conjugate"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"ADC chemistry"},{"id":"pharmacokinetics","kind":"term","name":"Pharmacokinetics (PK), half-life and exposure","aka":["pharmacokinetic","pharmacokinetics","PK/PD","pharmacodynamics","half-life","half life","exposure-response","exposure–response","drug exposure","AUC","Cmax","steady state","steady-state","bioavailability","oral bioavailability","drug-drug interaction","CYP3A4","food effect","therapeutic drug monitoring","TDM","flat dosing","weight-based dosing","body surface area","mg/m²","mg/kg","pharmacodynamic"],"tldr":"How a drug moves through the body: how much is absorbed, how high the blood level gets, how long it lasts (half-life) and how it is cleared. These numbers decide the dose, the schedule and whether a pill can be taken with food or other medicines.","summary":"Antibodies have half-lives of 2-4 weeks and are dosed every 2-6 weeks, often now at flat doses (pembrolizumab 400 mg q6w) rather than by weight; small molecules are dosed daily and interact with CYP3A4 inhibitors, acid suppressants and food; chemotherapy is dosed by body surface area with organ-function adjustments. Exposure-response analyses link drug levels to efficacy and toxicity and underpin Project Optimus's push to find optimal rather than maximal doses; therapeutic drug monitoring is used for busulfan, methotrexate and increasingly for TKIs. Radiopharmaceutical PK determines tumour versus kidney and marrow dose (dosimetry). Poor oral bioavailability has ended more than one promising drug's development.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Pharmacokinetics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Pharmacokinetics"}],"tags":[],"related":["dosimetry"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"release-criteria","kind":"term","name":"Product release criteria (radiopharmaceutical quality control)","aka":[],"tldr":"Before any batch of radioactive drug can be given to a patient, it has to pass a checklist of quality tests, such as being the right radioactive strength, sterile, and chemically pure.","summary":"Product release criteria are the specific quality-control tests and pass/fail limits a radiopharmaceutical must meet before it is dispensed or administered. Under USP General Chapter <825>, licensees preparing or compounding radiopharmaceuticals on site must complete a quality assessment before use, appropriate to the preparation, which can include radionuclidic purity, radiochemical purity, chemical purity, pH, and physical appearance, in addition to sterility and bacterial endotoxin testing for injectable preparations made from non-sterile or non-pyrogen-certified components. Compliance with these tests is not optional: the chapter states that quality testing is mandatory for validating radiochemical purity of the final product through to its beyond-use date, particularly whenever a preparation deviates even slightly from the manufacturer's kit directions.\n\nA representative numeric release criterion is the 99Mo/99mTc radionuclidic purity limit: USP monographs for 99mTc radiopharmaceuticals require that 99Mo not exceed 0.15 microcurie per millicurie of 99Tc-99m at the time of administration, a limit that must be recalculated forward in time because the 99Mo-to-99mTc ratio rises continuously as the shorter-lived daughter decays away faster than the parent. Generator eluates must also be tested for radionuclide \"breakthrough\" of the parent isotope under 10 CFR 35.204, with eluates exceeding the specified limits barred from use and any exceedance reported to the generator manufacturer.\n\nExcept for unopened manufacturer unit-dose containers, the final patient dose or ordered amount must be radioassayed in a dose calibrator immediately before release, with the measured activity mathematically decay-corrected to the scheduled administration (calibration) time; the assayed activity must fall within federal, state, and institutional tolerance limits of the prescribed activity. Radiopharmaceuticals should not be administered if any impurity level exceeds the package insert or USP monograph specification. Records of every preparation, including quality-control results and final disposition, must be retained and are the primary evidence a regulator or accreditor reviews to confirm release criteria were actually met before a dose reached a patient.","asOf":"2026-09-22","links":[{"label":"USP General Chapter <825>, Radiopharmaceuticals - Preparation, Compounding, Dispensing, and Repackaging","url":"https://www.pharmacy.la.gov/assets/docs/Staff/USP_825-Radiopharmaceuticals_2020-1201.pdf"},{"label":"USP General Chapter <825> Impact on Nuclear Medicine Technology Practice, J Nucl Med Technol 2020","url":"https://tech.snmjournals.org/content/jnmt/48/2/106.full.pdf"},{"label":"ACR-SPR-SNMMI practice parameter excerpt on assay and administration quality control","url":"https://gravitas.acr.org/PPTS/DownloadPreviewDocument?DocId=171"}],"tags":["USP <825>","quality control","GMP"],"related":["radiopharmacy-term","hot-lab","dose-calibrator","radiopharmaceutical-gmp-release","patient-release-criteria","tc-99m","mo-99"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation"},{"id":"prrt-term","kind":"term","name":"PRRT (peptide receptor radionuclide therapy)","aka":["PRRT","peptide receptor radionuclide therapy","177Lu-DOTATATE","lutetium DOTATATE","DOTATATE","DOTATOC","somatostatin analogue","somatostatin analogues","SSA","SSAs","SSTR-targeted","SSTR imaging","somatostatin receptor imaging","alpha PRRT"],"tldr":"A radioactive drug for neuroendocrine tumours: a small peptide that homes to the somatostatin receptor on the tumour cells carries lutetium-177, which irradiates them from within. Given four times, two months apart.","summary":"Neuroendocrine tumours overexpress somatostatin receptor 2, imaged with gallium-68 or copper-64 DOTATATE PET and treated first with cold somatostatin analogues (octreotide, lanreotide) for symptom and growth control. 177Lu-DOTATATE (NETTER-1, approved 2018) improved progression-free survival dramatically in midgut NETs and NETTER-2 (2024) moved it to first line in high-grade tumours; 177Lu-edotreotide (COMPETE) followed. Alpha-emitting versions (212Pb-DOTAMTATE, 225Ac-DOTATATE) are in phase 3 for PRRT-refractory disease. Toxicities are marrow suppression, kidney dose and a small risk of MDS. Together with radioiodine and PSMA therapy it defines the theranostic model.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Peptide_receptor_radionuclide_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Peptide_receptor_radionuclide_therapy"}],"tags":[],"related":["prrt","theranostics","dosimetry","radioiodine-therapy","alpha-vs-beta","ga-68","cu-64","lu-177","ac-225","pb-212"],"indications":["neuroendocrine"],"sections":[],"technologies":["radioligand-therapy","targeted-alpha-therapy"],"targets":["sstr2"],"drugs":["ga68-dotatate"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"psa-kinetics","kind":"term","name":"PSA kinetics: PSA doubling time and PSA density","aka":["PSA doubling time","PSADT","PSA velocity","PSA density","PSAD","PSA kinetics","PSA rise","rising PSA","biochemical recurrence PSA threshold","PSA nadir","PSA response","PSA50","PSA90","PSA progression"],"tldr":"How fast PSA is rising matters more than its level: a doubling time under ten months after surgery or radiotherapy, or under nine months in castration-resistant disease, marks the men whose cancer is moving quickly and who benefit from earlier hormone therapy or a PSMA scan, while PSA density (PSA divided by prostate volume) helps decide who needs a biopsy at all.","summary":"What is measured: the rate of change of prostate-specific antigen and its concentration relative to gland size. How: doubling time is calculated by log-linear regression from at least three values over at least three months; density is PSA (ng/mL) divided by prostate volume (mL) on MRI or ultrasound, with 0.15 (0.10 with MRI) the usual threshold. Confounders: 5-alpha-reductase inhibitors halve PSA, prostatitis raises it. What a result changes: after radical prostatectomy a PSA of 0.2 ng/mL or more defines biochemical recurrence, and the EAU splits it into low and high risk by a doubling time of a year or less or a Gleason grade group of 4 or 5, which sets the urgency of salvage radiotherapy and whether hormone therapy is added; PSMA PET is positive in most men above 0.5 ng/mL; in non-metastatic castration-resistant disease a doubling time of ten months or less was the entry criterion for SPARTAN (apalutamide), PROSPER (enzalutamide) and ARAMIS (darolutamide), which lengthened metastasis-free and overall survival; a density above 0.15 with a PI-RADS 3 lesion tips towards biopsy, and density is an entry criterion for active surveillance (PRIAS 0.2 or less); in metastatic castration-resistant disease a 50 percent PSA fall (PSA50) is a trial endpoint, and a PSA under 0.2 at seven months of hormone therapy predicts long survival. Where it matters: biochemical recurrence, low-risk, non-metastatic castration-resistant and metastatic castration-resistant prostate cancer.","asOf":"2026-09-17","links":[],"tags":[],"related":["psma-pet","enzalutamide"],"indications":["prostate-bcr","prostate-nmcrpc","prostate-mcrpc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"psa50","kind":"term","name":"PSA50 / PSA90 response","aka":[],"tldr":"PSA50 is the share of patients whose PSA falls by at least half on treatment, and PSA90 the share whose PSA falls by 90%.","summary":"PSA50 is the proportion of patients whose PSA falls by at least half on treatment, and PSA90 the proportion whose PSA falls by nine tenths or more. Both are standard early-efficacy read-outs in trials of metastatic castration-resistant prostate cancer, reported under the PCWG3 recommendations, and readers meet them in the VISION and TheraP radioligand trials and on the page for xaluritamig. A PSA response correlates with, but does not replace, radiographic progression-free survival and overall survival. The endpoint can also end a development programme early: a PSA90 futility analysis stopped masofaniten's phase 2. The term extends the PSA entry, which describes the underlying marker.","asOf":"2026-09-06","wikipedia":"https://en.wikipedia.org/wiki/Prostate-specific_antigen","links":[{"label":"PCWG3 trial design recommendations incl. PSA response reporting (Scher et al., J Clin Oncol 2016)","url":"https://doi.org/10.1200/JCO.2015.64.2702"}],"tags":[],"related":[],"indications":["prostate"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Endpoints"},{"id":"psma-rads","kind":"term","name":"PSMA-RADS (PSMA reporting and data system)","aka":[],"tldr":"A standard 1-to-5 scale that nuclear medicine doctors use to describe how likely a spot seen on a PSMA PET scan is to be prostate cancer, so different hospitals describe the same finding the same way.","summary":"PSMA-RADS version 1.0, proposed by Rowe, Pienta, Pomper and Gorin at Johns Hopkins in 2017-2018, is a structured reporting system for PSMA-targeted PET imaging modelled on other \"reporting and data systems\" such as BI-RADS. It assigns each lesion a category from 1 (benign, subdivided into 1A without uptake and 1B with uptake but known-benign) through 2 (likely benign, low-level uptake atypical for prostate cancer), 3A/3B/3C/3D (equivocal, warranting further work-up such as biopsy or 3-6 month follow-up imaging), 4 (intense uptake typical of prostate cancer but without a corresponding finding on conventional imaging) to 5 (intense uptake with a corresponding conventional-imaging finding, prostate cancer almost certainly present). Reports give up to five target lesions a PSMA-RADS category plus an overall scan score equal to the highest individual lesion score.\n\nInterobserver agreement studies on 18F-DCFPyL PET/CT found good-to-excellent agreement (intraclass correlation coefficients of 0.60-0.84 depending on lesion type), supporting its reproducibility across readers. A revised PSMA-RADS 2.0 has since been proposed, folding the 1A/1B split into a single benign category, allowing PSMA-RADS 3A/3B/3D lesions to be reclassified as 4 in patients with widespread metastatic disease, and adding a 5T subcategory for effectively treated metastases after systemic prostate cancer therapy.\n\nThe system is complementary to PSMA PET-guided treatment decisions (for example selecting patients for lutetium-177 or actinium-225 PSMA radioligand therapy) but is not itself a treatment-eligibility threshold; eligibility criteria used in trials such as VISION relied on separate PSMA-positivity rules.","asOf":"2026-09-22","links":[{"label":"Rowe SP, Pienta KJ, Pomper MG, Gorin MA. Proposal for a Structured Reporting System for PSMA-Targeted PET Imaging: PSMA-RADS Version 1.0. J Nucl Med 2018;59:479-485","url":"https://jnm.snmjournals.org/content/jnumed/59/3/479.full.pdf"},{"label":"Werner RA, et al. Interobserver Agreement for PSMA-RADS 1.0 on 18F-DCFPyL PET/CT. J Nucl Med (2018)","url":"https://jnm.snmjournals.org/content/jnumed/early/2018/09/06/jnumed.118.217588.full.pdf"},{"label":"PSMA-RADS: updated version 2.0 discussion (PMC, 2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11981304/"}],"tags":["reporting system","PSMA PET","structured reporting"],"related":["psma-pet","psma","ga68-psma-11","pylarify","pluvicto","prostate-mcrpc","vision","f-18","lu-177","ac-225"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"imaging"},{"id":"radiation-necrosis","kind":"term","name":"Radiation necrosis (brain)","aka":[],"tldr":"Death of brain tissue months to years after radiosurgery or high-dose brain radiotherapy, which can look exactly like tumour growing back on a scan.","summary":"Radiation necrosis affects a minority of patients after stereotactic radiosurgery to brain metastases and after high-dose treatment of gliomas, more often with larger volumes and with concurrent immunotherapy or targeted drugs. It causes swelling and symptoms that mimic progression; perfusion MRI, amino-acid PET and sometimes biopsy separate the two. Treatment is steroids, bevacizumab for refractory cases, and occasionally surgery or laser ablation.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Radiation_necrosis","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_necrosis"}],"tags":["radiation-wave1"],"related":[],"indications":["glioblastoma"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"radiation-safety-officer","kind":"term","name":"Radiation Safety Officer (RSO)","aka":[],"tldr":"Every US clinic or hospital that uses radioactive drugs must have one named, specially qualified person responsible for making sure radiation is used and stored safely.","summary":"Under US Nuclear Regulatory Commission rules (10 CFR 35.24), every licensee authorised for the medical use of byproduct material must appoint a Radiation Safety Officer (RSO) in writing, who agrees to be responsible for implementing the facility's radiation protection programme and for ensuring that radiation safety activities follow licensee-approved procedures and regulatory requirements. Management, through the RSO, remains accountable for the programme even though day-to-day duties are delegated.\n\nThe qualification pathway is set out in 10 CFR 35.900 (and its current successor, 35.50 for newer licenses): an individual can qualify either by board certification (for example the American Board of Health Physics, American Board of Radiology, American Board of Nuclear Medicine, or the Board of Pharmaceutical Specialties in Nuclear Pharmacy), or through a structured programme of at least 200 hours of classroom and laboratory training covering radiation physics and instrumentation, radiation protection, mathematics of radioactivity, radiation biology and radiopharmaceutical chemistry, plus one year of full-time supervised experience as a radiation safety technologist, or by already being an authorized user identified on the licensee's own license. A licensee may also appoint one or more Associate Radiation Safety Officers to support the RSO, though the RSO cannot delegate the ultimate authority or responsibility for the programme.\n\nThe RSO role sits alongside, and is distinct from, the Authorized User, who is the physician credentialed to prescribe and administer specific categories of radioactive drugs; a single individual can hold both roles if separately qualified for each. Agreement States (which license the majority of US medical radioactive material users) apply equivalent, NRC-compatible requirements under their own regulations.","asOf":"2026-09-22","links":[{"label":"10 CFR 35.900, Radiation Safety Officer (GovInfo, CFR)","url":"https://www.govinfo.gov/content/pkg/CFR-2004-title10-vol1/pdf/CFR-2004-title10-vol1-sec35-900.pdf"},{"label":"NRC: Authorized Individuals - Radiation Safety Officer and Associate RSO","url":"https://www.nrc.gov/materials/miau/med-use-toolkit/auth-individuals"},{"label":"eCFR: 10 CFR Part 35, Medical Use of Byproduct Material","url":"https://www.ecfr.gov/current/title-10/chapter-I/part-35"}],"tags":["NRC","10 CFR Part 35","radiation protection programme"],"related":["authorized-user","alara","nrc-licensing","hot-lab","radiopharmaceutical-gmp-release"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation"},{"id":"prostatectomy","kind":"term","name":"Radical prostatectomy","aka":["prostatectomy","robotic prostatectomy","robot-assisted prostatectomy","prostatectomies"],"tldr":"Removing the entire prostate gland and seminal vesicles for localised prostate cancer, now almost always with a robot.","summary":"One of three options for localised disease alongside radiotherapy and active surveillance; ProtecT showed identical 15-year prostate cancer mortality (~3%) across all three. Robot-assisted laparoscopic prostatectomy dominates in high-income countries with nerve-sparing techniques to reduce erectile dysfunction, but incontinence (5-20%) and impotence (30-70%) remain the main harms. PSA should become undetectable; a rise afterwards (biochemical recurrence) is imaged with PSMA PET and treated with salvage radiotherapy.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Prostatectomy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Prostatectomy"}],"tags":[],"related":[],"indications":["prostate"],"sections":[],"technologies":["psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"radiochemical-purity","kind":"term","name":"Radiochemical purity (RCP)","aka":[],"tldr":"A quality check on a radioactive drug that asks: of all the radioactivity in the vial, what fraction is actually in the correct, working chemical form, rather than stuck to the wrong molecule or floating free?","summary":"Radiochemical purity is the proportion, usually expressed as a percentage, of the total radioactivity in a radiopharmaceutical preparation that is present in the intended chemical form, that is, correctly bound to the targeting molecule in the right molecular position. It is measured by radio-HPLC or radio-thin-layer chromatography, comparing the area or counts of the desired peak to the total radioactive signal across all peaks, and it is a mandatory batch-release and stability test under pharmacopoeial standards such as the European Pharmacopoeia.\n\nRadiochemical impurities, most often free (unbound) radiometal or radiolysis breakdown products, have a different biodistribution from the intended drug and can degrade image quality in diagnostics or misdirect dose in therapeutics. EANM technical guidance generally asks for RCP above 95% for most diagnostic tracers, though some agents such as 99mTc-HMPAO tolerate lower purity (above 80%) because of their inherent chemistry. For 177Lu-labelled therapeutics, radiochemical purity typically starts near 98% at the end of synthesis and is tracked over the product's shelf-life because it falls with time owing to radiolysis, driven by beta particles from the decaying 177Lu generating reactive free radicals in the aqueous formulation; antioxidant 'radioprotectants' such as ascorbate and gentisic acid are added specifically to slow this decline (see Radiolysis).\n\nRadiochemical purity is distinct from radionuclidic purity, which asks whether the radioactivity comes from the correct radionuclide at all, and from chemical purity, which concerns non-radioactive contaminants.","asOf":"2026-09-22","links":[{"label":"EANM 2019 technologist guide: radiopharmacy, an update","url":"https://eanm.org/wp-content/uploads/2024/06/EANM_2019_TechGuide.pdf"},{"label":"EANM guideline on validation of analytical methods for radiopharmaceuticals (PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC7016057/"}],"tags":[],"related":["radionuclidic-purity","radiolysis","chelator-term","tc-99m","lu-177"],"indications":[],"sections":[],"technologies":["radiopharmaceutical-gmp-release","sterile-fill-finish"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"chemistry"},{"id":"radioiodine-term","kind":"term","name":"Radioiodine therapy (I-131)","aka":["radioiodine","radioactive iodine","radioiodine ablation","radioiodine therapy","I-131","131I","iodine-131","RAI-refractory","radioiodine-refractory","RAI-avid","radioiodine-avid","iodine-avid","iodine uptake","redifferentiation","recombinant TSH","rhTSH"],"tldr":"Swallowing a capsule of radioactive iodine after thyroid surgery: thyroid cells (including cancer cells) are the only ones that soak up iodine, so the radiation destroys leftover thyroid tissue and metastases while sparing everything else. It was the first targeted radiotherapy, in 1946.","summary":"Differentiated (papillary and follicular) thyroid cancer retains iodine uptake, so I-131 ablates remnant tissue after total thyroidectomy in intermediate- and high-risk patients and treats iodine-avid metastases; low-risk patients no longer need it (ESTIMABL2, IoN). Thyroglobulin and whole-body scans monitor for recurrence. 'Radioiodine-refractory' disease (about 5-15%, more in poorly differentiated and BRAF-mutant tumours) is treated with lenvatinib, sorafenib or targeted drugs for RET, NTRK and BRAF alterations, and MEK/BRAF inhibitors can restore iodine uptake ('redifferentiation'). Side effects are salivary gland damage, dry mouth and a small excess of secondary cancers at high cumulative doses.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Iodine-131","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Iodine-131"}],"tags":[],"related":["radioiodine-therapy","theranostics","prrt","i-131"],"indications":["thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":["sorafenib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"radiolysis","kind":"term","name":"Radiolysis (self-radiolysis of radiopharmaceuticals)","aka":[],"tldr":"A radioactive drug can damage itself: the radiation it gives off breaks apart water and other molecules in the vial, creating reactive fragments that attack the drug molecule and reduce how much of it is still working correctly by the time it reaches the patient.","summary":"Radiolysis is the chemical decomposition of a radiopharmaceutical caused by its own emitted radiation, primarily through the radiolysis of water in the formulation, which generates highly reactive free radicals (such as hydroxyl radicals) that go on to damage the targeting molecule or its chelator. It is distinct from radioactive decay of the radionuclide itself; radiolysis affects the chemical integrity of the drug molecule the radionuclide is attached to, and it is measured as a fall in radiochemical purity over time.\n\nRadiolysis is a particularly significant problem for high-activity, high-specific-activity therapeutic radiometal preparations such as 177Lu-labelled PSMA and somatostatin-receptor ligands, because beta particles emitted by 177Lu interact with the surrounding water to produce radicals that attack the peptide or chelator. Published data show 177Lu-PSMA-617 radiochemical purity falling from about 98% to roughly 80% within 24 hours at room temperature without adequate protection, and falling to single-digit percentages within 24 hours with no radioprotectant at all, whereas with adequate antioxidant protection and cold storage it can be kept above 95% for 48 hours or longer.\n\nRadiolysis is controlled in manufacturing and formulation by adding radioprotectant ('quencher') compounds, most commonly ascorbic acid/sodium ascorbate, often combined with gentisic acid or methionine, which scavenge the reactive radicals before they reach the drug molecule; by keeping the radioactive concentration below a set threshold (diluting the product); and by storing and transporting the finished product refrigerated or frozen. The FDA labels for Lutathera (177Lu-dotatate) and Pluvicto (177Lu-vipivotide tetraxetan) specify their gentisic acid and ascorbate/sodium ascorbate content and corresponding shelf-lives (78 hours and 120 hours respectively) as part of managing radiolysis.","asOf":"2026-09-22","links":[{"label":"PMC: radiolysis-associated decrease in radiochemical purity of 177Lu-radiopharmaceuticals and comparison of quenchers","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9967390/"},{"label":"Bioconjugate Chemistry: ascorbic acid as a buffer agent and radiolytic stabilizer for metalloradiopharmaceuticals","url":"https://pubs.acs.org/doi/10.1021/bc034109i"}],"tags":[],"related":["radiochemical-purity","chelator-term","lu-177"],"indications":[],"sections":[],"technologies":["radiopharmaceutical-gmp-release","sterile-fill-finish","lu177-radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"chemistry"},{"id":"radionuclidic-purity","kind":"term","name":"Radionuclidic purity","aka":[],"tldr":"A check that the radioactivity in a vial really comes from the intended radioactive element, and not from some other radioactive contaminant left over from how it was made.","summary":"Radionuclidic purity is the proportion of the total radioactivity in a preparation that is due to the stated, intended radionuclide, as opposed to any other radioactive species (radionuclidic impurities) that may have formed alongside it during production. It concerns the identity of the radioactive atoms themselves, not their chemical form (that is radiochemical purity) or the mass of the labelled compound (that is specific activity).\n\nRadionuclidic impurities typically arise from side reactions in the target material during cyclotron or reactor production, or from parent/daughter contamination in a generator system. A well-known example is a technetium-99m generator eluate, where a small amount of the parent molybdenum-99 can break through with the technetium-99m and must be kept below regulatory limits; another is actinium-225 production, where the accompanying actinium-227 impurity level is a live manufacturing and regulatory concern. For fluorine-18 FDG, IAEA guidance specifies acceptance criteria including a measured half-life within 105-115 minutes and no less than 99% of gamma emissions attributable to 18F, verified by gamma-ray spectrometry, which distinguishes radionuclides by the characteristic energies they emit.\n\nRadionuclidic purity is a mandatory release test because an unexpected radionuclide contributes unplanned dose to the patient (with its own, possibly very different, half-life and emission type) and can also corrupt quantitative imaging or dosimetry that assumes a single, known decay scheme.","asOf":"2026-09-22","links":[{"label":"IAEA: radionuclidic identity and purity (educational materials)","url":"https://nucleus.iaea.org/sites/accelerators/Modern%20AKP%20Site%20Assets/Educational%20Materials;%20Radioisotope%20and%20Radiopharmaceutical%20Production%20using%20a%20Medical%20Cyclotron/6-Quality%20Control%20and%20Batch%20Release/Radionuclidic%20Identity%20and%20Purity.pdf"},{"label":"IAEA: cyclotron produced radionuclides, guidance on facility design and production (18F acceptance criteria)","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/Pub1515_Web.pdf"}],"tags":[],"related":["radiochemical-purity","specific-activity","f-18","tc-99m","mo-99","ac-225"],"indications":[],"sections":[],"technologies":["radiopharmaceutical-gmp-release","radionuclide-generators-kits","cyclotron-isotope-production"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics"},{"id":"extravasation-radiopharmaceutical","kind":"term","name":"Radiopharmaceutical extravasation","aka":[],"tldr":"Sometimes an injected radioactive tracer or treatment leaks into the tissue around the vein instead of going into the bloodstream. For scanning tracers this usually just affects image quality; for treatment doses it can occasionally injure the skin and needs prompt attention.","summary":"Extravasation is the inadvertent leakage of an injected radiopharmaceutical into the tissue surrounding the injection site instead of the vein. For diagnostic tracers labelled with 99mTc, 123I, 18F or 68Ga, extravasation is common but rarely causes tissue injury; a systematic review of more than 3,000 reported diagnostic extravasations found fewer than 0.1% caused symptoms requiring clinical follow-up, and none of the 99mTc/123I/18F/68Ga cases needed intervention. Its main practical consequence for diagnostics is degraded image quantification (altered biodistribution and reduced injected activity reaching the target), which matters most for quantitative studies such as dosimetry or lymphoscintigraphy.\n\nExtravasation of a therapeutic radiopharmaceutical is potentially more serious because the higher administered activity and longer-range or higher-LET emissions can cause localised soft-tissue injury, including skin necrosis in severe cases. SNMMI guidance instructs staff to stop the infusion immediately if resistance is felt, swelling appears, or the patient reports pain, and to document the estimated infiltrated volume and site. Symptoms warranting evaluation by a plastic surgeon include swelling greater than 2.5 cm, numbness, blanched or translucent skin, tight or leaking skin, discoloration or bruising, and any circulatory or nerve impairment. Management strategies described in the literature (cooling versus warming, elevation, and rarely surgical excision) are not strongly evidence-based, and EANM/SNMMI procedure guidelines give only limited practical advice, largely confined to the 90Y-ibritumomab tiuxetan (Zevalin) guideline, which recommends local hyperthermia, elevation and gentle massage.\n\nUnder US NRC policy, extravasations have historically been treated as a practice-of-medicine issue rather than a reportable medical event, since they occur even with technically correct injections; however, an extravasation that leads to unintended permanent functional damage can be reportable as a medical event under 10 CFR 35.3045(b), and SNMMI and the NRC's Advisory Committee on the Medical Uses of Isotopes have discussed whether CTCAE grade 3-4 tissue injury from a therapeutic extravasation should trigger notification requirements similar to other medical events.","asOf":"2026-09-22","links":[{"label":"SNMMI: Use of Radiopharmaceuticals guideline (clinical use and administration, extravasation)","url":"https://captions.snmmi.org/common/Uploaded%20files/Web/Clinical%20Practice/Procedure%20Standards/2025/Use%20of%20Radiopharm_FINAL.pdf"},{"label":"van der Pol J, et al. Consequences of radiopharmaceutical extravasation and therapeutic interventions: a systematic review, Eur J Nucl Med Mol Imaging 2017","url":"https://link.springer.com/article/10.1007/s00259-017-3675-7"},{"label":"SNMMI position statement and comments to NRC on extravasation rulemaking, 2023","url":"https://sites.snmmi.org/common/Uploaded%20files/Web/Advocacy%20and%20Initiatives/2023-09-07/NRC%20Comments%20on%20Extravasations%20Rulemaking%209-1-2023.pdf"}],"tags":["injection safety","adverse event","NRC"],"related":["radiopharmaceutical-gmp-release","in-vivo-dosimetry","gamma-probes-dose-calibrators","b-dose-optimisation","f-18","ga-68","tc-99m","i-123","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"safety"},{"id":"radiopharmacy-term","kind":"term","name":"Radiopharmacy (practice and discipline)","aka":[],"tldr":"Radiopharmacy is the specialised branch of pharmacy that prepares radioactive drugs safely, correctly and on time, since these medicines decay and can't simply be reordered from a shelf.","summary":"Radiopharmacy is the pharmacy specialty concerned with the procurement, compounding, quality control, dispensing and record-keeping of radioactive drugs. In the United States its compounding and quality standards are set out in USP General Chapter <825> \"Radiopharmaceuticals - Preparation, Compounding, Dispensing, and Repackaging\", which requires that prepared or compounded radiopharmaceuticals meet identity, quality and purity standards from manufacturer labelling, USP monographs or other appropriate sources; that non-sterile compounded components undergo a sterilisation step; that components not certified pyrogen-free undergo bacterial endotoxin testing; and that the final dose or ordered amount be radioassayed in a dose calibrator except for unopened manufacturer containers.\n\nA central radiopharmacy concept is the beyond-use date (BUD): the date and time beyond which a compounded, prepared, repackaged or dispensed radiopharmaceutical must not be administered, determined from the stability of quality attributes such as sterility, radiochemical purity and radionuclidic purity. USP <825> sets reference BUDs of 1 hour for immediate-use sterile radiopharmaceuticals and 99mTc-labelled red blood cells, 6 hours for radiolabelled blood components, 10 hours for direct infusion systems, and 24 hours for radiopharmaceuticals prepared and dispensed under classic sterile compounding conditions. Radionuclidic purity requirements also change with time since calibration: for example, USP monographs for 99mTc radiopharmaceuticals cap the 99Mo radionuclidic impurity at 0.15 microcurie of 99Mo per millicurie of 99Tc-99m at the time of administration, which must be recalculated forward because the ratio increases continuously as the shorter-lived 99mTc decays faster than its 99Mo parent.\n\nDay-to-day radiopharmacy practice includes assaying generator eluate for radionuclidic breakthrough (regulated under 10 CFR 35.204), preparing kits under aseptic technique in the hot lab, performing radiochemical purity testing (commonly thin-layer or paper chromatography) before a preparation is released for patient use, and maintaining records of preparation date and time, activity, component lot numbers, quality-control results and final disposition. The discipline sits at the intersection of pharmacy compounding law, NRC/Agreement State radioactive-materials licensing, and nuclear medicine clinical practice.","asOf":"2026-09-22","links":[{"label":"USP General Chapter <825> Radiopharmaceuticals - Preparation, Compounding, Dispensing, and Repackaging (briefing/full text)","url":"https://www.nihs.go.jp/dnfi/pdf/RI_PDF/USP3-1.pdf"},{"label":"USP General Chapter <825> Impact on Nuclear Medicine Technology Practice, J Nucl Med Technol 2020","url":"https://tech.snmjournals.org/content/jnmt/48/2/106.full.pdf"},{"label":"2025 USP <825> Radiopharmaceuticals Addendum","url":"https://content.govdelivery.com/attachments/WADOH/2025/01/25/file_attachments/3142978/2025%20USP%20825%20Radiopharmaceuticals%20Addendum.pdf"}],"tags":["USP <825>","compounding","quality control"],"related":["hot-lab","dose-calibrator","release-criteria","radiopharmacy-network","radiopharmaceutical-gmp-release","sterile-fill-finish","tc-99m","mo-99"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"regulation"},{"id":"radiotherapy","kind":"term","name":"Radiotherapy","aka":["radiation therapy","radiation treatment","radiation","irradiation","irradiated","radiotherapy fractions","fractionation","hypofractionated","chemoradiotherapy","chemoradiation","radiation oncology","radiation oncologist","radiosensitiser","radiosensitizer","radiosensitive","radioresistant","external beam","radiation oncologists","radiosensitisers"],"tldr":"Using high-energy X-rays or particles to damage the DNA of cancer cells in a precisely aimed volume of the body. On its own it cures early prostate, larynx, cervix and skin cancers, it is combined with chemotherapy in head and neck, lung, oesophageal and rectal cancers, and about half of all cancer patients receive it.","summary":"Modern radiotherapy shapes beams to the tumour from several angles (IMRT, image-guided and stereotactic techniques) so that the tumour gets a lethal dose while surrounding tissue gets much less; treatment is usually split into daily fractions over one to seven weeks to let normal tissue repair, though ultra-short courses (SBRT) are increasingly used. It is a local therapy, curative on its own in early prostate, larynx, cervix and skin cancers, combined with chemotherapy in head and neck, lung, oesophageal and rectal cancers, and used after surgery to sterilise the operative bed. Protons and carbon ions spare more normal tissue; radiation may also help immunotherapy by releasing tumour antigens (the abscopal effect), and radioligand therapy delivers radiation internally through a targeting molecule.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Radiation_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Radiation_therapy"}],"tags":[],"related":[],"indications":[],"sections":[],"technologies":["radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Clinic basics"},{"id":"relative-biological-effectiveness","kind":"term","name":"Relative biological effectiveness (RBE)","aka":[],"tldr":"A number that says how much more (or less) biological damage a given amount of one type of radiation causes compared with the same physical amount of a reference radiation. Alpha particles are typically several times more damaging, gray for gray, than the beta particles used in more established radioligand therapies.","summary":"Relative biological effectiveness (RBE) is defined as the ratio of the absorbed dose of a reference radiation (conventionally x-rays, gamma rays, or a beta emitter) to the absorbed dose of a test radiation required to produce an identical biological effect under otherwise identical conditions: RBE = D(reference)/D(test) for the same endpoint. Unlike the fixed, consensus-based radiation weighting factor (wR) used in the regulatory quantity equivalent dose, RBE is an empirically measured quantity that varies with the specific biological endpoint studied (cell survival, organ toxicity, tumour control), the dose and dose rate, the cell type, and oxygen tension, so a single RBE value cannot be assumed to apply across all contexts.\n\nFor targeted alpha therapy, RBE values for cell-kill endpoints are commonly reported in the range of roughly 3 to 8 relative to external-beam or beta reference radiation, though for stochastic cancer-induction endpoints regulatory bodies use a flat wR of 20 for alpha particles, illustrating why RBE and wR are not interchangeable. In actinium-225 versus lutetium-177 dosimetry specifically, experimental work using DNA double-strand-break markers has reported RBE values around 5, and this figure has been used as a practical multiplier to convert measured absorbed dose in gray into an RBE-weighted dose estimate when comparing alpha and beta radioligand therapies or predicting organ toxicity.\n\nRBE is central to interpreting and comparing dosimetry across the beta-to-alpha pairing strategy in radioligand therapy (for example, sequencing lutetium-177 PSMA therapy with actinium-225 PSMA therapy), because a modest gray value from an alpha emitter can correspond to a much larger biologically effective dose than the same gray value from a beta emitter.","asOf":"2026-09-22","links":[{"label":"PMC: redefining relative biological effectiveness in the context of alpha-particle therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3984880/"},{"label":"PMC: estimation of relative biological effectiveness of 225Ac compared to 177Lu","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10495309/"}],"tags":[],"related":["linear-energy-transfer","equivalent-dose","alpha-vs-beta","lu-177","ac-225"],"indications":[],"sections":[],"technologies":["targeted-alpha-therapy","radioligand-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"dosimetry"},{"id":"renal-protection-amino-acids","kind":"term","name":"Renal protection with amino acid co-infusion","aka":[],"tldr":"Before a peptide receptor radionuclide therapy infusion, patients are given an IV drip of two amino acids, lysine and arginine, which reduces how much radioactivity the kidneys reabsorb and hold onto, protecting kidney function.","summary":"Radiolabelled peptides such as DOTATATE are filtered by the kidney and partly reabsorbed in the proximal tubule, where they can be retained long enough to deliver a clinically significant radiation dose; the kidney is the dose-limiting organ for peptide receptor radionuclide therapy. Co-infusing positively charged amino acids, most commonly a mixture of L-lysine and L-arginine, competitively blocks this tubular reabsorption. The joint IAEA/EANM/SNMMI practical guidance on PRRT describes protocols using 25 g lysine plus 25 g arginine (a 50 g total \"cocktail\") diluted in 1-2 litres of normal saline and infused over about 4 hours, started 30-60 minutes before the radiopeptide and continued for at least 3-4 hours afterwards; some centres extend protection over 2-3 days post-therapy for additional renal sparing.\n\nPublished reductions in renal absorbed dose from amino acid co-infusion range from roughly 9% to 65% depending on amino acid dose, infusion duration, and how long protection is continued after therapy, with a commonly cited average reduction of around 40%. Higher lysine doses (for example 75 g) reduce renal uptake further but cause more side effects such as nausea and vomiting, so 25 g lysine plus 25 g arginine is regarded as the standard trade-off. Hyperkalaemia, nausea and vomiting are the main side effects of the amino acid infusion itself, and hyperosmotic solutions should be avoided in patients with cardiac insufficiency because of the risk of volume overload and electrolyte disturbance.\n\nDespite renal protection, long-term creatinine clearance loss of roughly 3-4% per year has been reported after 177Lu-DOTATATE (compared with a steeper roughly 7% per year after the older 90Y-DOTATOC), and PRRT is generally avoided in patients with a glomerular filtration rate below 30-40 mL/min. A large single-institution retrospective series of over 1,200 patients receiving amino acid-protected PRRT found no clear evidence of long-term nephrotoxicity, though prospective, randomised confirmation across centres is limited. Alternatives such as arginine-only infusion or Gelofusine/succinylated gelatin, and newer approaches such as para-aminohippurate (PAH) co-infusion, are being studied as ways to reduce side effects while preserving nephroprotection.","asOf":"2026-09-22","links":[{"label":"IAEA, EANM, SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours, PMC","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3622744/"},{"label":"Long-term Nephrotoxicity after PRRT: Myth or Reality, PMC 2024","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10758070/"},{"label":"Bergsma H, et al. Safety and Efficacy of Para-Aminohippurate Coinfusion for Nephroprotection, J Nucl Med 2024","url":"https://jnm.snmjournals.org/content/65/6/931"}],"tags":["nephroprotection","PRRT","supportive care"],"related":["prrt","itm-11","lutathera","neuroendocrine","cytopenias","gray-unit","lu-177","y-90"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"safety"},{"id":"salivary-gland-toxicity","kind":"term","name":"Salivary gland toxicity (xerostomia) from PSMA radioligand therapy","aka":[],"tldr":"PSMA radioligand therapy can dry out the mouth because normal salivary glands pick up a small amount of the drug along with the tumour. It's very common but usually mild, and is one of the main reasons patients ask about the treatment beforehand.","summary":"Prostate-specific membrane antigen is expressed at low levels on normal salivary gland tissue as well as on prostate cancer cells, so PSMA-targeted radioligand therapies deliver an incidental radiation dose to the salivary glands. In the pivotal VISION trial of lutetium-177 vipivotide tetraxetan (Pluvicto), dry mouth (xerostomia) occurred in 39% of patients receiving Pluvicto plus best standard of care versus 0.5-1% on standard of care alone (any grade); no grade 3-4 xerostomia was reported in VISION. Dosimetry sub-studies found a mean salivary gland absorbed dose of roughly 0.5-0.6 Gy/GBq, which is towards the lower end of a wide reported range (0.5-1.9 Gy/GBq), and translates to roughly 25-30 Gy after a full six-cycle course at 7.4 GBq per cycle.\n\nThe FDA label for Pluvicto lists dry mouth among the most common adverse reactions (occurring in \\u226520% of patients) and specifies dose modifications for recurrent or higher-grade dry mouth: for grade 2, withhold until improvement and consider a 20% dose reduction; for grade 3, withhold and reduce by 20% to 5.9 GBq; recurrent grade 3 dry mouth after one dose reduction is grounds for permanent discontinuation. In the combined PSMAfore/VISION safety population reported in a later label update, dry mouth of any grade occurred in around 46-61% of patients, reflecting longer follow-up and pooled populations.\n\nManagement is largely supportive: hydration, sugar-free gum or lozenges to stimulate residual saliva, avoiding alcohol-based mouthwash and irritant foods, and monitoring for secondary dental disease, since dry mouth increases caries risk. Xerostomia typically improves gradually after treatment ends. External radioprotective strategies (external cooling, salivary gland-sparing infusion techniques) are under investigation but are not yet standard of care.","asOf":"2026-09-22","links":[{"label":"FDA label: Pluvicto (lutetium Lu 177 vipivotide tetraxetan), accessdata.fda.gov","url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215833s021s024lbl.pdf"},{"label":"EMA: Pluvicto assessment report (EPAR)","url":"https://www.ema.europa.eu/en/documents/assessment-report/pluvicto-epar-public-assessment-report_en.pdf"},{"label":"[177Lu]Lu-PSMA-617 (Pluvicto): The First FDA-Approved Radiotherapeutic for mCRPC, PMC 2022","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9608311/"}],"tags":["adverse effect","PSMA therapy","quality of life"],"related":["pluvicto","lu177-psma-it","psma","prostate-mcrpc","vision","psmafore","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"safety"},{"id":"sdh-deficiency","kind":"term","name":"SDH deficiency (SDHB immunohistochemistry loss)","aka":["SDH-deficient","SDH-deficient GIST","SDHB immunohistochemistry","SDHB loss","SDHB-negative","SDHx","SDHx mutation","SDHA","SDHC epimutation","SDHC promoter methylation","succinate dehydrogenase deficiency","Carney-Stratakis syndrome","Carney triad","KIT/PDGFRA wild-type GIST","hereditary paraganglioma syndrome","SDH-deficient renal cell carcinoma"],"tldr":"Loss of the succinate dehydrogenase enzyme, shown by a negative SDHB stain, marks a small family of tumours (some stomach GISTs, paragangliomas and phaeochromocytomas, a rare kidney cancer) that are often inherited, occur in young people, ignore imatinib and grow slowly; the stain is the trigger for germline testing of the whole family.","summary":"What is measured: loss of the mitochondrial succinate dehydrogenase complex. How: SDHB immunohistochemistry on the tumour (loss of granular cytoplasmic staining whichever subunit is mutated; SDHA staining is lost only with SDHA mutation), followed by germline and tumour sequencing of SDHA, SDHB, SDHC, SDHD and SDHAF2 and, if negative, testing for SDHC promoter methylation (the epimutation behind the Carney triad). Where it occurs: 5 to 7 percent of GISTs (almost all gastric, in young and often female patients, multifocal, epithelioid, with nodal metastases and an indolent course; Carney-Stratakis syndrome pairs them with paragangliomas), 30 to 40 percent of paragangliomas and phaeochromocytomas (SDHB carriers have the highest metastatic risk), SDH-deficient renal cell carcinoma and some pituitary adenomas. What a result changes: an SDH-deficient GIST does not respond to imatinib because it does not depend on KIT, sunitinib and regorafenib help modestly, temozolomide is under study because of the tumours' hypermethylation, surgery is kept conservative because multifocality and nodal disease are the rule, and follow-up is lifelong; a germline finding leads to cascade testing, whole-body MRI surveillance every two to three years and plasma metanephrines; metastatic paraganglioma is treated with lutetium-177 DOTATATE or iodine-131 MIBG, and HIF-2 alpha inhibitors such as belzutifan are in trials. Where it matters: GIST, imatinib-resistant GIST and the rare childhood cancers page.","asOf":"2026-09-17","links":[],"tags":[],"related":["sunitinib","temozolomide","lutathera","lu-177","i-131"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},{"id":"sentinel-lymph-node-biopsy","kind":"term","name":"Sentinel node biopsy","aka":["sentinel lymph node biopsy","sentinel lymph node","sentinel node","sentinel lymph node mapping","SLNB"],"tldr":"Finding and removing the first one or two lymph nodes a tumour drains to, to see whether cancer has spread, instead of removing the whole nodal basin.","summary":"A dye or radioactive tracer (technetium tilmanocept, indocyanine green, blue dye) injected at the tumour travels to the 'sentinel' node, which is removed and examined. If it is clear, the remaining nodes are almost certainly clear and a full dissection with its lymphoedema risk is avoided. Standard in breast cancer, melanoma (from ~0.8 mm Breslow), endometrial and vulval cancers and increasingly oral cavity cancer; even positive sentinel nodes often no longer trigger full axillary dissection (Z0011, SENOMAC).","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Sentinel_lymph_node","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Sentinel_lymph_node"}],"tags":[],"related":["tilmanocept-tc99m"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"specific-activity","kind":"term","name":"Specific activity and molar activity","aka":[],"tldr":"A measure of how much of a radioactive drug is genuinely radioactive versus how much is ordinary, non-radioactive filler of the same molecule. Higher specific activity means more radioactive atoms are packed onto the targeting molecules, so fewer 'cold' (non-radioactive) copies compete for the same receptors.","summary":"Specific activity is the activity of a radionuclide divided by the total mass of the element (or the labelled compound) present, expressed in units such as GBq/mg; molar activity is the same idea per mole (GBq/µmol) and is the preferred term when the labelled molecule, not the element, is what matters clinically. Because no radiolabelling reaction is perfectly efficient, every batch of a radiopharmaceutical contains some non-radioactive ('cold') copies of the same targeting molecule alongside the radioactive ones, and specific activity quantifies that ratio.\n\nThe practical stakes are receptor saturation: for a receptor-targeted tracer or therapy (an SSTR or PSMA ligand, for example), the cold carrier competes with the radiolabelled molecule for a limited number of binding sites, so low specific activity can reduce tumour uptake per unit of injected mass. The qualitative terms carrier-free, no-carrier-added (n.c.a.) and carrier-added describe roughly how much stable-isotope carrier is present without stating a number; a 2018 international nomenclature consensus recommends always reporting the measured specific or molar activity rather than relying on these qualitative labels alone.\n\nSpecific activity is determined experimentally, commonly by HPLC (comparing the radioactive peak to a UV mass calibration curve) or, theoretically, from the decay constant and the assumption of no carrier at all. It is a batch-release and formulation parameter tracked in GMP manufacture of PET and therapeutic radiometal agents, and it is specified in clinical trial protocols for tracers such as 18F-fluoromisonidazole or 89Zr-antibody conjugates.","asOf":"2026-09-22","links":[{"label":"IAEA TECDOC: determination of specific activity","url":"https://www-pub.iaea.org/MTCD/Publications/PDF/TE-1856web.pdf"},{"label":"International consensus nomenclature for radiopharmaceutical chemistry (PMC)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5852186/"}],"tags":[],"related":["no-carrier-added","chelator-term","f-18","zr-89"],"indications":[],"sections":[],"technologies":["pet-tracer-manufacturing","radiopharmaceutical-gmp-release","sstr-pet","psma-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics"},{"id":"suv","kind":"term","name":"Standardised uptake value (SUV)","aka":[],"tldr":"The standardised uptake value (SUV) is a number for how brightly a spot lights up on a PET scan.","summary":"The standardised uptake value (SUV) is the number radiologists use to say how brightly a spot lights up on a PET scan. It is tissue radioactivity normalised to the injected dose and body weight, and SUVmax is the most widely used version. Values are affected by the scanner, the uptake time and blood glucose, and the PERCIST response criteria use SUL, a lean-body variant, instead. The term belongs to the PET (positron emission tomography) and FDG PET technology entries and to the Fludeoxyglucose F-18 (FDG) drug record, and it is referenced by the Cancer metabolism pathway, the Warburg effect, the Society of Nuclear Medicine and Molecular Imaging, and ideas on de-acidifying tumours so T cells can work and on a phase 0 fund using microdoses and imaging.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Standardized_uptake_value","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Standardized_uptake_value"}],"tags":[],"related":["f-18"],"indications":[],"sections":[],"technologies":["pet","fdg-pet"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Diagnostics & imaging"},{"id":"tare","kind":"term","name":"TARE / SIRT (radioembolisation with yttrium-90)","aka":["TARE","SIRT","radioembolisation","radioembolization","Y-90","Y90","yttrium-90","selective internal radiation therapy","90Y microspheres"],"tldr":"Injecting tiny radioactive glass or resin beads into the liver's artery so they lodge in the tumour and irradiate it from inside.","summary":"Yttrium-90 microspheres (20-60 µm) deliver beta radiation over a few millimetres with a 64-hour half-life, treating hepatocellular carcinoma, colorectal liver metastases and neuroendocrine liver metastases. Randomised trials against sorafenib (SARAH, SIRveNIB) showed no survival gain but better tolerability; radiation segmentectomy, which delivers ablative doses to a small segment, achieves outcomes close to ablation. Dosimetry now individualises the activity (DOSISPHERE). Chosen over TACE when portal vein thrombus is present.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Selective_internal_radiation_therapy","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Selective_internal_radiation_therapy"}],"tags":[],"related":["y-90"],"indications":["hcc","neuroendocrine"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Procedures"},{"id":"theranostic-pair-term","kind":"term","name":"Theranostic pair","aka":[],"tldr":"A matched set of two radioactive drugs built on the exact same molecule: one labelled with a radioactive tag good for taking pictures (a PET scan), the other labelled with a different radioactive tag good for treatment, so the scan predicts where the treatment will go.","summary":"A theranostic pair is a diagnostic and a therapeutic radiopharmaceutical that share the same, or a near-identical, targeting molecule (peptide, small molecule or antibody), so that the biological distribution seen on the diagnostic scan is expected to closely mirror where the therapeutic radiopharmaceutical will localise and deliver radiation dose. The classic and historically first example is 123I/131I sodium iodide, where both agents follow the identical physiological pathway (the sodium-iodide symporter) into the thyroid. The current dominant paradigm labels the same peptide or small-molecule vector with two different chemical elements: a positron emitter for PET imaging (commonly gallium-68, sometimes copper-64 or fluorine-18) and a therapeutic emitter for treatment (commonly lutetium-177 for beta therapy, or actinium-225 for alpha therapy), examples being 68Ga/177Lu-DOTATATE for somatostatin-receptor-positive neuroendocrine tumours and 68Ga/177Lu-PSMA-617 (or PSMA-I&T) for prostate cancer.\n\nBecause the imaging and therapeutic agents in a \"different-element pair\" are chemically distinct compounds rather than isotopes of the same element, their pharmacokinetics can diverge somewhat (different positron/beta energies, different in vivo stability of the chelate, sometimes different affinity), so a positive diagnostic scan is a necessary but not perfect predictor of therapeutic biodistribution; this is one rationale for post-therapy SPECT/CT imaging with the therapeutic radionuclide itself, when it emits an imageable gamma (as 177Lu does), to confirm actual dose delivery. Lutetium-177 is unusual in being \"theranostic on its own\": its beta emission treats while its co-emitted 113/208 keV gamma photons allow SPECT imaging of the same injection, without needing a separate diagnostic radionuclide.\n\nOther reported or developing theranostic pairs include 43/44Sc/47Sc, 64Cu/67Cu, 86Y/90Y, 152Tb/161Tb, 89Zr/177Lu or 225Ac (for CAIX and other antibody-based pairs), and 68Ga/225Ac or 213Bi combinations for alpha therapy planning. The theranostic pair concept underlies the pairing entries in this graph (for example psma-pet-to-rlt and sstr-pet-to-prrt) and is the organising principle behind most modern radioligand development programmes, which typically design a diagnostic and a therapeutic analogue of a new ligand together from the outset.","asOf":"2026-09-22","links":[{"label":"Expanding Theranostic Radiopharmaceuticals for Tumor Diagnosis and Therapy, PMC 2021 (theranostic pair table)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8780589/"},{"label":"Molecular theranostics: principles, challenges and controversies, J Med Radiat Sci 2025","url":"https://onlinelibrary.wiley.com/doi/full/10.1002/jmrs.836"},{"label":"Implications of physics, chemistry and biology for dosimetry calculations using theranostic pairs, Theranostics 2022","url":"https://www.thno.org/v12p0232.htm"}],"tags":["theranostics","radiochemistry","drug pairing"],"related":["theranostics","psma-pet-to-rlt","sstr-pet-to-prrt","ga68-dotatate","ga68-psma-11","lutathera","pluvicto","f-18","ga-68","i-123","cu-64","zr-89","sc-44","y-86","lu-177"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"therapy"},{"id":"theranostics","kind":"term","name":"Theranostics","aka":["theranostic"],"tldr":"Using the same targeting molecule for a diagnostic scan and a therapy, so you treat exactly what you can see.","summary":"Theranostics uses the same targeting molecule for a diagnostic scan and for therapy, so clinicians treat exactly what they can see. The established pairs are gallium-68 or fluorine-18 PSMA imaging with lutetium-177 or actinium-225 PSMA therapy, gallium-68 DOTATATE with lutetium-177 DOTATATE, and iodine-123 with iodine-131, and one chemistry thereby enables patient selection, dosimetry and response assessment. The concept links the Radioligand therapy (beta emitters), Targeted alpha therapy and PSMA PET technologies with Somatostatin receptor PET, Radioiodine therapy and the pairings PSMA PET to PSMA radioligand therapy and SSTR PET to PRRT. It is referenced by the Prostate cancer, Thyroid cancer and Neuroendocrine tumours entries and by Clarity Pharmaceuticals.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Theranostics","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Theranostics"}],"tags":[],"related":["f-18","ga-68","i-123","lu-177","ac-225","i-131"],"indications":[],"sections":[],"technologies":["radioligand-therapy","psma-pet","targeted-alpha-therapy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},{"id":"thrombocytopenia","kind":"term","name":"Thrombocytopenia","aka":["thrombocytopaenia","low platelets","platelet count","platelet transfusion","bleeding risk","grade 3-4 thrombocytopenia","immune thrombocytopenia","ITP","thrombopoietin receptor agonist","platelet transfusions"],"tldr":"Too few platelets, the blood cells that form clots, caused by chemotherapy or by the cancer in the marrow. Mild cases cause bruising; severe cases (under 10-20 × 10⁹/L) risk serious bleeding and need platelet transfusions.","summary":"Common with carboplatin, gemcitabine, temozolomide, lurbinectedin, PARP inhibitors (niraparib especially), radioligand therapies and in leukaemia and myeloma; it limits dose more often than neutropenia for some regimens because no growth factor is routinely used (romiplostim and avatrombopag are being trialled). Grade 4 is <25 × 10⁹/L. It also complicates anticoagulation for cancer-associated thrombosis and procedures such as biopsies and central line placement. Cirrhosis with portal hypertension causes chronic thrombocytopenia that constrains liver cancer treatment, and immune thrombocytopenia is an immune-related adverse event of checkpoint inhibitors.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/Thrombocytopenia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Thrombocytopenia"}],"tags":[],"related":["cytopenias","anaemia"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Side effects"},{"id":"time-activity-curve","kind":"term","name":"Time-activity curve (TAC)","aka":[],"tldr":"A graph of how much of an injected radioactive drug is present in an organ or tumour at different times after the injection. It shows the drug arriving, peaking and then clearing out, and it is the raw data that personalised radiation-dose calculations are built from.","summary":"A time-activity curve (TAC) plots measured radioactivity (or activity concentration) in a region of interest, an organ, a tumour, blood, or the whole body, against time after a radiopharmaceutical is administered. It is generated from a series of quantitative images (dynamic PET frames, or sequential SPECT/CT or planar scans taken at several time points after a therapeutic injection) or from direct sampling such as blood or excreta counting.\n\nThe shape of the TAC reflects both the physical decay of the radionuclide and the biological uptake, retention and clearance of the labelled compound in that tissue; separating these two contributions is why dosimetry needs the effective half-life rather than the physical half-life alone. Integrating the area under a TAC over the intended dose-integration period gives the time-integrated activity (historically 'cumulated activity'), and dividing that by the administered activity gives the time-integrated activity coefficient, the direct input to the MIRD dose equation. Because TAC shape is usually inferred from only a handful of imaging time points (commonly three to four samples spanning a few hours to about a week after 177Lu therapy) and then fitted with an exponential or other analytical function, the number, timing and spacing of these samples, and the choice of fitting model, are recognised as major, site-dependent sources of variability in radioligand-therapy dosimetry.\n\nAccurate TAC measurement matters clinically because both under- and over-sampling can bias the estimated absorbed dose to kidneys, marrow or tumour, which in turn affects dosimetry-guided activity prescription and estimates of nephrotoxicity or haematotoxicity risk.","asOf":"2026-09-22","links":[{"label":"PMC: understanding time-activity curve and time-integrated activity coefficient calculation in radiopharmaceutical therapy","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12464796/"},{"label":"EANM guidance document: dosimetry for first-in-human studies","url":"https://link.springer.com/content/pdf/10.1007/s00259-024-06640-x.pdf"}],"tags":[],"related":["mird-formalism","decay-correction","effective-half-life","activity-prescription","lu-177"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","in-vivo-dosimetry"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"dosimetry"},{"id":"time-of-flight-pet","kind":"term","name":"Time-of-flight (TOF) PET","aka":[],"tldr":"A more precise kind of PET scanner that measures the tiny difference in arrival time between the two flashes of light produced by each radioactive decay, which helps pinpoint where in the body the decay happened and produces clearer, less noisy images, especially in larger patients.","summary":"In PET, a positron annihilates with an electron to produce two 511 keV photons travelling in almost exactly opposite directions; the scanner detects both photons in coincidence and knows the decay occurred somewhere along the line connecting the two detectors (the line of response), but conventional PET has no information about where along that line. Time-of-flight (TOF) PET measures the small difference in the two photons' arrival times with high-precision timing electronics and fast scintillator crystals, which localises the annihilation point to a smaller segment of the line of response: the positional uncertainty is Δx = c x Δt / 2, where c is the speed of light and Δt is the scanner's coincidence timing resolution.\n\nModern clinical TOF-PET scanners achieve coincidence timing resolutions in the range of roughly 200-400 picoseconds, corresponding to a spatial localisation of roughly 3-6 cm along the line of response; this does not by itself improve the intrinsic spatial resolution of the image (still around 4-5 mm, set by detector and reconstruction factors), but it substantially reduces statistical noise during image reconstruction because each detected event only needs to be redistributed across a much shorter segment of possible locations rather than the full line of response. The resulting gain in image signal-to-noise ratio is proportional to the square root of the object size (patient girth) divided by the timing resolution, so the benefit of TOF is greatest in larger patients.\n\nClinically, TOF capability improves lesion detectability, allows shorter scan times or lower injected activity for the same image quality, and is now standard on modern PET/CT and total-body PET systems used for oncological imaging, including PSMA, SSTR and FDG PET.","asOf":"2026-09-22","links":[{"label":"PMC: update on time-of-flight PET imaging","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4287223/"},{"label":"PMC: advances in time-of-flight PET","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4747834/"}],"tags":[],"related":["attenuation-correction","partial-volume-effect"],"indications":[],"sections":[],"technologies":["pet","pet-ct","nuclear-medicine-hardware","total-body-pet-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"physics"},{"id":"tumour-hypoxia","kind":"term","name":"Tumour hypoxia","aka":[],"tldr":"Regions of a tumour that have outgrown their blood supply and are short of oxygen. They resist radiotherapy and some chemotherapy, and drive the tumour to become more aggressive.","summary":"Fast-growing tumours have chaotic, leaky blood vessels, leaving pockets of cells living on very little oxygen. Hypoxic cells need up to three times the radiation dose to be killed, switch on HIF-driven survival programmes, become more invasive and are selected for genomic instability. Hypoxia can be imaged with PET tracers, measured by gene signatures and targeted with sensitisers, hypoxia-activated drugs, hyperthermia and dose escalation.","asOf":"2026-09-17","wikipedia":"https://en.wikipedia.org/wiki/Tumor_hypoxia","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Tumor_hypoxia"}],"tags":["radiation-wave1"],"related":[],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biology basics"},{"id":"tumour-to-background-ratio","kind":"term","name":"Tumour-to-background ratio (TBR)","aka":[],"tldr":"A simple number that says how much brighter a tumour looks on a scan compared with the normal tissue around it or nearby. A higher ratio makes a tumour easier to see and count.","summary":"Tumour-to-background ratio (TBR), also called tissue-to-background or lesion-to-background ratio, divides a measure of tracer uptake in a lesion (typically SUVmax or SUVpeak) by a measure of uptake in a reference region, which may be a fixed organ such as liver or blood pool, gluteal muscle, the contralateral normal tissue, or the tissue immediately surrounding the lesion (\"local TBR\"). Because PET and SPECT images are reconstructed and displayed with contrast-dependent scaling, TBR is a practical proxy for lesion conspicuity and is used both qualitatively (as a component of the Krenning score and PSMA-RADS) and quantitatively in response criteria.\n\nIn amino acid PET for brain tumours, the RANO/EANM/SNMMI/EANO consensus (PET RANO 1.0) defines PET-positive tumour as any voxel with uptake at least 1.6 times the mean background activity measured in a reference region of normal frontal lobe, and tracks change in TBRmax and TBRmean over time as response criteria (for example, an increase of 30% or more in TBRmax defines PET-based progression). The choice of reference tissue changes the number materially: a lesion's ratio to liver, muscle, and the immediately surrounding tissue can differ by an order of magnitude, so any reported TBR should state which reference region and which SUV metric were used.\n\nTBR is sensitive to technical factors including reconstruction algorithm, attenuation correction, and time after injection, so serial comparisons for treatment response are only valid when acquisition protocol is held constant.","asOf":"2026-09-22","links":[{"label":"Radiopaedia: tissue to background ratio","url":"https://radiopaedia.org/articles/tissue-to-background-ratio?lang=us"},{"label":"PET-based response assessment criteria for diffuse gliomas (PET RANO 1.0), Lancet Oncology group report","url":"https://escholarship.org/content/qt7480171k/qt7480171k_noSplash_75492753629cf0018dd0db00b41434a0.pdf"}],"tags":["quantitative imaging","SUV","response assessment"],"related":["suv","quantitative-imaging-biomarkers","krenning-score","psma-rads","fdg-pet"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"imaging"}]