Open evaluation

Technetium-99m has a six-hour half-life, so it cannot be shipped and stored. Hospitals receive a 99Mo/99mTc generator loaded with the 65.94-hour parent molybdenum-99 and elute the daughter once or twice a day, adding it to a cold kit for that day's scans.

• six-hour / 6.0067-hour
• generator / moly cow / elute
• molybdenum-99 / 99mo
• cold kit / on site / just-in-time

Its 6.65-day half-life allows international shipping, its 0.5-2 mm beta range matches small-to-medium deposits, and its 208 keV gamma emission is imageable, so the treating injection can also be used for post-therapy SPECT and dosimetry.

• 6.65-day / 6.65 day
• beta range / beta
• 208 kev
• spect / dosimetry

Historic supply is milked from a legacy thorium-229 stockpile at milligram scale; a 2023 Journal of Nuclear Medicine analysis put world supply near 63 GBq (1.7 Ci) a year, enough for 100-200 patients, against hundreds to thousands of curies if approved drugs scale. Accelerator routes (thorium-232 spallation, 226Ra(p,2n)225Ac) are being industrialised by the DOE Tri-Lab effort and commercial cyclotron capacity.

• thorium-229 / 229th
• 63 gbq / 1.7 ci / 100-200 patients
• spallation / 226ra / accelerator
• tri-lab / brookhaven / los alamos / oak ridge

Most molybdenum-99 comes from a handful of ageing research reactors such as BR2 and the HFR. Because technetium-99m cannot be stockpiled, an unplanned outage — the HFR's October 2024 structural fault, for example — feeds straight through to delayed or cancelled scans.

• research reactor / reactors
• br2 / hfr / safari-1
• outage / shutdown / shortage
• delayed / cancelled

Gallium-68, as 68Ga-DOTATATE or DOTATOC: a 67.7-minute positron emitter eluted from a 68Ge/68Ga generator or made on a cyclotron, which images the same somatostatin receptor that 177Lu-DOTATATE then irradiates.

• gallium-68 / 68ga
• dotatate / dotatoc
• generator / cyclotron
• 67.7-minute / one-hour

Fluorine-18 is the workhorse PET radionuclide, made by a regional cyclotron each morning from oxygen-18 enriched water. Its 109.8-minute half-life is long enough to ship unit doses to nearby hospitals but short enough that about a third of the activity is lost every hour, so the scan list has to be scheduled around the delivery.

• 109.8-minute / 109.8 minute
• cyclotron
• third of the activity / every hour
• fdg / psma / amyloid

Ac-225 decays through six short-lived daughters to stable bismuth-209, releasing a net four alpha particles per decay (a 'nanogenerator'), but worldwide 229Th/225Ac-derived supply is only about 63 GBq (1.7 Ci) per year, enough for just 100-200 patients. Bi-213, a 45.6-minute half-life daughter of Ac-225, has to be milked from that same scarce Ac-225 stock via a generator typically eluted every two to three hours in clinical use, and because only the final alpha of the chain is captured, using it consumes 225Ac less efficiently per alpha particle delivered than using 225Ac directly.

• nanogenerator
• 63 gbq / 1.7 ci / 100-200 patients
• 45.6 minutes / 45.6-minute
• two to three hours
• less efficiently

Radium-223 dichloride (Xofigo) is a calcium mimetic that concentrates in areas of increased bone turnover such as osteoblastic bone metastases, then decays mostly by emitting alpha particles (95.3% of emitted energy) with a range under 100 micrometres in tissue, so the dose is deposited within roughly the width of a few cells of the bone surface, largely sparing the adjacent marrow. It was the first alpha-emitting radiopharmaceutical to gain FDA and EMA approval, on the strength of the ALSYMPCA trial's overall-survival benefit in metastatic castration-resistant prostate cancer.

• calcium mimetic / xofigo
• 95.3%
• 100 micrometres
• alsympca
• castration-resistant prostate cancer

Th-227 is an alpha emitter with an 18.7-day half-life that decays through a five-alpha cascade, via 223Ra, 219Rn, 215Po, 211Pb, 211Bi and 211Po, to stable 207Tl/207Pb, releasing about 32.4 MeV of alpha energy per decay chain, making it an in vivo generator of its own daughter, radium-223. Because 227Th is obtained from the same growing 227Ac/227Th/223Ra generator column used for commercial radium-223 (ORNL, PNNL, Rosatom, Bayer), its co-produced daughter 223Ra must be removed and accounted for as a radioactive contaminant.

• 18.7-day
• five-alpha cascade
• in vivo generator
• 32.4 mev
• 227ac/227th/223ra

At-211 has a 7.2-hour half-life and decays entirely by alpha emission, and because of that half-life it must be produced close to where it will be used and cannot be stockpiled or shipped over long distances. As of the mid-2020s only a handful of cyclotrons worldwide routinely produce clinical-grade 211At, including Copenhagen, Arronax in Nantes, Duke University, the University of Washington and Ionetix in Michigan (shipping since September 2026), which is why supply is the binding constraint.

• 7.2-hour
• cannot be stockpiled
• shipped over long distances
• ionetix
• 28-29.5 mev

Terbium-161 shares much of lutetium-177's chemistry, since both are trivalent lanthanides suited to DOTA-type chelators, so it can be substituted directly into existing DOTATATE, DOTATOC and PSMA-617-type ligands, with a similar tissue range of about 0.7 mm and a half-life of 6.95 days, close to 177Lu's 6.65 days. The difference is that Tb-161 also produces a large yield of low-energy conversion and Auger electrons, roughly 2.3 electrons above 3 keV per decay, which may give it more damage to single cells and micrometastases than lutetium-177 through those additional short-range electrons.

• 6.95 days / 6.95-day
• 0.7 mm
• auger
• 2.3 electrons
• dota-type chelators

Iodine-131 works because thyroid follicular cells and well-differentiated thyroid cancer retain the sodium/iodide symporter, so oral 131I concentrates selectively in thyroid tissue, remnant tissue after thyroidectomy, and iodine-avid metastases wherever they have spread, delivering an internal beta dose with very little effect on the rest of the body. It has a physical half-life of 8.02-8.04 days and has been used for benign thyroid disease and differentiated thyroid cancer for more than 70 years, remaining a WHO essential medicine.

• sodium/iodide symporter
• 8.02 / 8.04
• who essential medicine
• more than 70 years

90Y is a near-pure beta emitter with only a small pair-production fraction, so imaging its distribution usually relies on a separate technetium-99m-labelled surrogate lung-shunt scan, whereas 166Ho emits an 81 keV gamma (about 6.6-6.7% abundance) suitable for SPECT/CT and is also visible on MRI because of its paramagnetic properties, so the same microsphere product used for a diagnostic 'scout' dose and the therapeutic dose can both be imaged directly. 166Ho's shorter 26.8-hour half-life also concentrates over 90% of its dose within about 4 days, compared with 94% of the 90Y dose delivered within about 11 days.

• 81 kev
• scout
• 26.8
• 94%
• paramagnetic / mri

Copper-64 and copper-67 are chemically identical, so a chelator-conjugated agent labelled with the PET isotope 64Cu (half-life 12.7 hours) has the same chelation chemistry and biodistribution as the same agent labelled with the therapeutic 67Cu (half-life 61.8-62 hours), avoiding the surrogate mismatch inherent in most other theranostic pairs. This same-element pairing is used clinically with agents such as SAR-bisPSMA and SARTATE.

• 12.7 hours / 12.7-hour
• 61.8
• surrogate mismatch
• sar-bispsma
• sartate

Mo-99 is the most fragile: some 90-95% of global supply historically came from just five ageing research reactors not designed for continuous isotope production, so an unplanned outage such as the October 2024 shutdown of the Dutch HFR directly worsened shortages of both 99Mo and 99mTc. Ge-68/Ga-68 generators are made at only a small number of high-energy cyclotron facilities and historically had GMP-grade lead times as long as 18 months. Rb-82 needs no cyclotron at all, using a strontium-82 generator with a roughly 25-day parent half-life, but US regulations cap 82Sr and 85Sr breakthrough at 0.02 microcurie and 0.2 microcurie per millicurie of 82Rb, and generators require daily quality control.

• 90-95%
• october 2024
• 18 months
• 0.02 microcurie
• 25-day

FDG PET uses 18F-fluorodeoxyglucose, a radioactive sugar analogue taken up through GLUT transporters and trapped by hexokinase, exploiting the Warburg effect by which most cancers burn glucose fast. It is weak in prostate cancer, low-grade neuroendocrine tumours, mucinous cancers and some breast cancers, and infection and inflammation are also hot on the scan.

• 18f-fluorodeoxyglucose / fdg
• warburg
• glut
• prostate cancer / neuroendocrine tumours
• infection and inflammation

PSMA PET detects biochemical recurrence at a PSA below 0.5 ng/mL, far earlier than CT or bone scan. But around 10% of patients have PSMA-negative disease, and uptake in ganglia and salivary glands can be mistaken for tumour.

• 0.5 ng/ml
• ct or bone scan
• 10%
• ganglia / salivary glands

SSTR PET (68Ga-DOTATATE, 68Ga-DOTATOC or 64Cu-DOTATATE) is mandatory for staging, for selecting patients for PRRT when the Krenning score is 3 or more or uptake is above liver, and for detecting occult primaries. FDG PET complements it in high-grade or dedifferentiated disease, producing a 'flip-flop' pattern between the two scans.

• 68ga-dotatate / dotatate
• prrt
• krenning score
• flip-flop
• dedifferentiated / high-grade

FAPI PET uses quinoline-based FAP inhibitors (FAPI-04, FAPI-46, FAPI-74) labelled with 68Ga or 18F to image cancer-associated fibroblasts rather than glucose metabolism, and head-to-head series show it is superior to FDG in pancreatic, gastric, HCC and peritoneal disease. Registrational trials for 68Ga-FAPI-46 and 18F-FAPI-74 are underway.

• fapi-04 / fapi-46 / fapi-74
• cancer-associated fibroblasts
• pancreatic / gastric / hcc
• 68ga / 18f

123I-MIBG scintigraphy with SPECT is the standard staging scan in neuroblastoma and is read with the Curie score; 18F-MFBG PET is partly replacing it. The same targeting is used therapeutically as 131I-MIBG.

• 123i-mibg
• curie score
• 18f-mfbg / mfbg pet
• 131i-mibg

The 99mTc-MDP bone scan is a SPECT study, and an ambiguous hot spot on the planar image is hard to place anatomically. SPECT/CT fuses that gamma-camera study with a CT on one gantry, so the CT corrects for attenuation and turns an ambiguous spot on a bone scan into a rib fracture or a metastasis, and it also maps a sentinel node to the correct basin before surgery.

• 99mtc-mdp
• attenuation
• rib fracture
• sentinel
• spect/ct / spect-ct

PET/MRI adds no ionising radiation from the MRI component, so the combined dose is lower than PET/CT, which is why it is valuable in paediatrics and patients needing repeated scans. The trade-off is that PET/MRI is limited by cost, the small number of scanners, long acquisition times, and harder attenuation correction because MRI does not directly measure tissue density, whereas PET/CT has been the default clinical standard since 2001.

• no ionising radiation
• paediatrics
• attenuation correction
• since 2001

Total-body PET systems image the entire body in one field of view with roughly forty times the sensitivity of conventional scanners, enabling minute-long scans and tracer doses a fraction of the usual, which makes asymptomatic screening technically conceivable for the first time. But there is no evidence of mortality benefit, and incidentalomas, cost and radiation argue against it; the near-term value is in dosimetry, paediatrics and pharmacokinetic research instead.

• forty times / 40-fold / 40 times
• no evidence of mortality benefit
• incidentalomas
• dosimetry
• asymptomatic screening

Quantitative SPECT converts counts into absolute activity concentration in becquerels per millilitre using CT-based attenuation correction, scatter correction and resolution recovery within an iterative reconstruction, then a system-specific calibration factor. The choice of scatter-correction weighting materially affects accuracy: using default rather than object-optimised scatter weighting has been reported to underestimate activity by roughly 8-22%, so cross-calibration against a traceable dose calibrator with a uniform cylindrical phantom is required before the images can be trusted.

• becquerels per millilitre / bq/ml
• scatter correction / scatter-correction
• 8-22%
• cross-calibration
• cylindrical phantom

The aPROMISE deep-learning platform segments the prostate gland on PSMA PET in roughly 15 seconds compared with 30-45 minutes for manual contouring, with a Dice similarity coefficient of about 0.89 versus an inter-radiologist DSC of about 0.91. A comparative reader study found similarly high intra- and inter-reader agreement against histopathology for both the AI tool and a standard PACS viewer, and the AI automatically segmented about 92% of consensus lesions.

• apromise
• 15 seconds
• 30-45 minutes
• dice similarity coefficient / dsc
• 92%

CT is a fast 3D X-ray showing size and shape; PET shows biology by tracking where a radioactive tracer accumulates (for example glucose uptake with FDG or a specific protein such as PSMA). PET/CT combines both.

• x-ray / anatom / shape / size
• tracer / radioactive / biolog / metabol
• glucose / fdg / psma
• pet/ct / combine / both

The activated fibroblasts (FAP) in tumour stroma, present in more than 90% of epithelial indications, giving high contrast in pancreatic, gastric, HCC, and peritoneal disease where FDG is weak; it is not yet approved.

• fibroblast / fap / stroma
• pancrea / gastric / peritoneal / hcc / liver
• contrast / background / sensitiv
• not yet approved / registration / trial / investigational

177Lu-DOTATATE (Lutathera) was tested as first-line therapy in grade 2-3 neuroendocrine tumours in NETTER-2, whereas the original NETTER-1 trial that led to approval was a second-line study.

• netter-2
• netter-1
• grade 2-3
• 177lu-dotatate / lutathera

Yes: actinium-225 and lead-212 alpha-emitter agents such as 225Ac-PSMA-617 are in phase 3 development, and alpha therapy given after beta (177Lu-PSMA) failure has produced responses in PSMA-refractory disease.

• 225ac-psma-617 / actinium-225
• phase 3
• psma-refractory
• alpha therapy after beta failure / after beta failure

Radioligand therapies are mostly given at fixed activities rather than planned to an absorbed dose, unlike external radiotherapy. Post-treatment SPECT or PET imaging at several time points is instead used to calculate absorbed doses to tumours and organs at risk after the fact, and dose-escalation trials guided by kidney and marrow dosimetry are now testing whether dosing can be personalised.

• fixed activities
• spect / pet
• kidney and marrow / marrow dosimetry
• dose escalation / dose-escalation

The EANM 2022 guideline recommends three SPECT/CT acquisitions between 24 hours and 7 days after the first therapy cycle, with at least two days between the final two time points, reducing to a single acquisition at a matched time point for subsequent cycles. The region of interest is drawn to include the full renal cortex and medulla but exclude the renal pelvis.

• 24 hours and 7 days / 24 hours to 7 days
• eanm
• renal cortex and medulla / cortex and medulla
• single acquisition

DOTA's rigid octadentate cavity is sized for smaller lanthanide-like ions, so complexing a large Ac3+ ion (1.12 A ionic radius) is inefficient and needs heating to 80-95C. Macropa is an 18-membered diaza-crown-6 macrocycle with 'reverse size selectivity' that binds large ions like Ac3+ more tightly than small ones, and it complexed essentially all of a 26 kBq 225Ac spike within 5 minutes at room temperature, versus only about 10% for DOTA under the same conditions.

• reverse size selectivity
• 80-95 / 80–95°c
• 5 minutes
• 1.12

Alpha decay imparts a large recoil energy, roughly 100-200 keV, to the daughter nucleus - about a thousand times bigger than a chemical bond - so the daughter breaks free of its chelator on essentially every decay. For actinium-225, decaying through francium-221 and bismuth-213, the freed daughters redistribute to the kidneys (roughly 18-35% ID/g at 5-15 minutes) and other organs, and renal toxicity from 213Bi is a recognised dose-limiting concern.

• 100-200 kev
• francium-221 / 221fr
• 18-35
• renal toxicity

Pretargeting separates the antibody from the radionuclide: an unlabelled antibody carrying a bio-orthogonal handle is injected first and allowed 24-72 hours to accumulate at the tumour and clear from the circulation, then a small, rapidly clearing radiolabelled ligand is injected to ligate onto the antibody handle at the tumour, while unbound radioligand is excreted quickly, sharply cutting exposure to blood, marrow and normal tissue.

• 24-72 hours
• bio-orthogonal / bio-orthogonal handle
• tetrazine / iedda / trans-cyclooctene
• marrow

In advanced hepatocellular carcinoma, the randomised SARAH and SIRveNIB trials of yttrium-90 microsphere radioembolisation versus sorafenib were negative for overall survival, though they showed better tolerability and response. Personalised dosimetry in DOSISPHERE-01 and radiation segmentectomy in LEGACY instead established curative-intent use of TARE in early-stage disease.

• sarah / sirveni
• overall survival / os
• dosisphere-01
• legacy

Radium-223 (Xofigo) is the only approved alpha-emitter therapy, used for bone metastases, while actinium-225 and lead-212 agents such as 225Ac-PSMA-617, 225Ac-DOTATATE/RYZ101 and 212Pb-DOTAMTATE/AlphaMedix are still in phase 3 development for other cancers.

• radium-223 / xofigo
• bone metastases
• phase 3
• 212pb-dotamtate / alphamedix

Monte Carlo is regarded as the reference-standard method for internal dosimetry, simulating decay and particle transport through a voxelised patient anatomy within the MIRD formalism. Organ-level comparisons between GATE-derived Monte Carlo and traditional MIRD/OLINDA S-value dosimetry have shown roughly a 2% difference in total organ absorbed dose, and cross-code validation studies (GATE, GAMOS, MCNP6) found agreement typically within about 1-5% for self-organ S-values across isotopes including Lu-177, I-131 and Y-90.

• reference-standard / reference standard
• mird
• 2%
• gate / gamos / mcnp6

Pluvicto (lutetium-177 vipivotide tetraxetan, 177Lu-PSMA-617) is a radioactive drug that seeks out PSMA on prostate cancer cells, and requires a positive PSMA PET scan before starting. It is given as six cycles every 6 weeks, with side effects including xerostomia, cytopenias and the need for renal monitoring.

• psma
• six cycles / every 6 weeks
• psma pet positiv
• xerostomia

Patients need a Ga-68 DOTATATE PET scan (Netspot) to confirm SSTR-positive disease, and this PET changes management in about a third of patients; it is required before Lu-177 DOTATATE (Lutathera) therapy. Lutathera itself is dosed at 7.4 GBq every 8 weeks for 4 doses, given with an amino acid infusion to protect the kidneys.

• netspot / ga-68 dotatate / gallium-68 dotatate
• changes management in about a third
• 7.4 gbq
• amino acid infusion

Radium-223 (Xofigo) is a calcium mimetic that homes to bone metastases like calcium, given intravenously to men with symptomatic castration-resistant prostate cancer confined to bone without visceral disease; ALSYMPCA showed an overall survival benefit of 14.9 versus 11.3 months, and it became the first alpha-emitting drug ever approved, in 2013. Before it, samarium-153 lexidronam (Quadramet) and strontium-89 (Metastron) were the bone-pain radiopharmaceuticals used, though radium-223 and PSMA radioligands have since taken most of their role.

• calcium mimetic
• 14.9 / 11.3
• first alpha-emitting drug
• samarium-153 / quadramet / metastron / strontium-89

The ERA 223 trial showed an excess of fractures when radium-223 was combined with abiraterone, so that combination is now contraindicated without bone protection; PEACE III later showed combining radium-223 with enzalutamide plus bone-protecting agents was positive for radiographic progression-free survival and overall survival.

• era 223 / era223
• excess fractures / excess of fractures
• contraindicated
• peace iii / peace-iii

PSMA PET tracers split by isotope and production: gallium-68 gozetotide (PSMA-11) is made on site from a germanium-68 generator or cyclotron, while 18F agents like piflufolastat (Pylarify) allow central manufacture and shipping, competing with other 18F agents on distribution and bladder clearance. From 2020 these PSMA-targeted tracers, with higher sensitivity at low PSA and longer half-lives, took over most recurrence imaging from Choline C-11, which had a 20-minute half-life confining it to cyclotron sites, and largely displaced fluciclovine F-18.

• 68ga / gallium-68
• 18f / fluorine-18
• central manufacture
• choline c-11 / choline c 11 / choline-c11

Fludeoxyglucose F-18 (FDG) is the radioactive sugar tracer used in almost every cancer PET scan, approved by the FDA in 1994 and gaining its oncology indication in 2000 to assess abnormal glucose metabolism and help evaluate malignancy. Its weaknesses are uptake in inflammation and poor sensitivity for indolent or low-glucose tumours, which is why target-specific tracers have been developed.

• 1994
• 2000
• glucose metabolism
• inflammation

Yes: sodium fluoride F-18 uptake is a marker of bone turnover, not malignancy, so degenerative disease, fracture healing and other benign remodelling can be false positives, and correlation with CT or MRI is standard practice. It is most often used to detect osteoblastic bone metastases from prostate and breast cancer, where it offers higher sensitivity and better spatial resolution than technetium-99m bone scintigraphy.

• bone turnover
• false positive
• fracture healing
• technetium-99m bone scintigraphy / technetium

Amyloid PET tracers like florbetapir show beta-amyloid plaque density, but a positive scan indicates moderate to frequent plaques, a pattern also seen in some cognitively normal older adults, so it does not by itself establish an Alzheimer's diagnosis. Tau PET (flortaucipir/Tauvid) instead shows the density and distribution of aggregated tau neurofibrillary tangles, and a positive scan supports an Alzheimer's diagnosis only in conjunction with clinical and other diagnostic evaluation, so the two scans give complementary information.

• beta-amyloid / amyloid
• cognitively normal older adults
• tau neurofibrillary tangles / neurofibrillary tangles
• clinical and other diagnostic evaluation

DaTscan (ioflupane I-123) is a SPECT scan that visualises dopamine transporters in the striatum, helping differentiate essential tremor from tremor due to Parkinson's disease, multiple system atrophy or progressive supranuclear palsy, though it cannot distinguish between those three. It can also help differentiate probable dementia with Lewy bodies from Alzheimer's disease, though it cannot separate Lewy body dementia from Parkinson's disease dementia.

• dopamine transporter
• essential tremor
• dementia with lewy bodies
• striatal / striatum

Diagnostic iobenguane I-123 (AdreView) scintigraphy is used to confirm MIBG uptake in neuroblastoma and phaeochromocytoma before treatment, while high-dose 131I-MIBG therapy then delivers radiation from inside the MIBG-avid tumour cells, with a response rate of about 30-40% in relapsed or refractory neuroblastoma but myelosuppression requiring stem-cell support at doses of 12 mCi/kg or more. The therapeutic iobenguane I-131 product Azedra, approved in 2018 for phaeochromocytoma and paraganglioma, was discontinued by its maker in 2024, leaving compounded low-specific-activity 131I-MIBG or lutetium-177 dotatate as alternatives.

• 30-40% / 30 - 40%
• stem-cell support / stem cell support
• azedra
• discontinued

NETTER-1 randomised 231 people with midgut neuroendocrine tumours to 177Lu-Dotatate or high-dose octreotide. At 20 months, progression-free survival was 65.2% with the radioligand against 10.8% with octreotide, and the response rate was 18% against 3%. The result supported the 2018 approvals of Lutathera.

• 65.2% / 65.2
• 10.8% / 10.8
• 18%
• lutathera

PSMAfore met its primary radiographic progression-free survival endpoint with a large effect for 177Lu-PSMA-617 over a switch of androgen receptor pathway inhibitor. But overall survival was confounded by crossover of most control patients, so only crossover-adjusted analyses favour the radioligand, meaning the survival benefit is not a clean randomised comparison.

• radiographic progression-free survival / rpfs
• crossover
• confounded
• approval in the pre-chemotherapy setting

ALSYMPCA randomised 921 men with symptomatic bone-metastatic castration-resistant prostate cancer to radium-223 or placebo, met its primary overall survival endpoint and reduced skeletal events. It was a single pivotal trial, and the later ERA 223 trial combining radium-223 with abiraterone was harmful, so use is now restricted to monotherapy in bone-predominant disease.

• 921
• overall survival
• era 223
• monotherapy

In PRINCE, among 37 men a PSA decline of 50% or more occurred in 76%, and the objective response rate in those with measurable disease was 70%. Toxicity followed each drug's own profile: xerostomia, fatigue and pruritus were common but mostly grade 1-2, while grade 3 immune-related events such as colitis, pancreatitis and myasthenia gravis occurred in 30% of patients, with no grade 4 events or treatment-related deaths.

• 76%
• objective response rate
• colitis
• 30%

COMPETE randomised 309 people with gastroenteropancreatic neuroendocrine tumours to 177Lu-edotreotide or everolimus. It met its primary progression-free survival endpoint with a significantly higher response rate, but the interim overall survival trend was not significant, so the win is on progression-free survival only so far.

• 309
• everolimus
• progression-free survival
• not significant

SPLASH randomised 412 men and met its primary radiographic progression-free survival endpoint for 177Lu-PNT2002 over a switch of androgen receptor pathway inhibitor. But the interim overall survival analysis was numerically unfavourable, with 46 percent of events and 84 percent crossover, so Lantheus deprioritised a US filing pending mature data.

• radiographic progression-free survival / rpfs
• 46 percent
• 84 percent
• deprioritised / deprioritized

Among 162 randomised men, adding LuPSMA to enzalutamide improved PSA progression-free survival (13.0 vs 7.8 months, HR 0.43) at the interim analysis. At longer follow-up (median 34 months), overall survival also favoured the combination, with a median of 34 versus 26 months and a hazard ratio of 0.55.

• hr 0.43 / 0.43
• hr 0.55 / 0.55
• 34 vs 26 / 34 months
• 13.0 vs 7.8 / 13.0

Among 130 randomised men, giving 177Lu-PSMA-617 before docetaxel produced undetectable PSA in 41% versus 16% with docetaxel alone, and improved PSA progression-free survival (31 vs 20 months), with grade 3-4 toxicity comparable between arms.

• 41%
• 16%
• 31 vs 20 / 31 months
• docetaxel

PSMAddition randomised 1,144 men with metastatic hormone-sensitive prostate cancer to Pluvicto plus hormone therapy or standard care alone, and met its primary radiographic progression-free survival endpoint at ESMO 2025. Overall survival trended favourably but remained immature, and severe adverse events were more common, so whether early use improves survival or only delays progression is still open.

• 1,144 / 1144
• radiographic progression-free survival / rpfs
• immature
• severe adverse events

TheraP randomised 200 men, selected by PSMA and FDG PET, to 177Lu-PSMA-617 or cabazitaxel after docetaxel. It met its primary endpoint with a PSA response of at least fifty percent in 66 percent of men against 37 percent, with fewer side effects, but overall survival was similar after crossover, so the survival equivalence with cabazitaxel is the nuance that matters for sequencing.

• 66 percent
• 37 percent
• cabazitaxel
• survival equivalence

Technetium-99m, used in about two-thirds of nuclear medicine procedures, is generated from molybdenum-99, which has a 66-hour half-life and cannot be stockpiled, so the whole chain has to run near-continuously and just-in-time. About 95% of global Mo-99 supply comes from a handful of ageing research reactors, and when one such as the HFR shuts down, as it did in October 2024, it tightens Tc-99m availability in Europe and North America within days.

• 66 hours / 66-hour
• 95%
• just-in-time / near-continuous
• hfr

Legacy thorium-229 'cow' generators at four sites worldwide yield roughly 63 GBq (1.7 Ci) of actinium-225 a year, which a 2025 review estimates is enough for only 100 to 200 patient treatments globally, against research and trial demand alone estimated at around 185 GBq (5 Ci) a year.

• 63 gbq / 1.7 ci
• 100 to 200
• 185 gbq / 5 ci
• thorium-229

In June 2024 RayzeBio paused new-patient enrolment in the phase 3 ACTION-1 trial of RYZ101 (225Ac-DOTATATE) specifically because it could not secure enough actinium-225, citing a single global supplier for the trial; patients already enrolled continued treatment while the company worked to bring on-site production online.

• action-1
• ryz101
• single global supplier / single supplier
• 225ac-dotatate / actinium-225 dotatate

No-carrier-added Lu-177 can only be made by neutron irradiation of ytterbium-176 enriched above 96-99%, and only about one in 5,000 atoms in the target ends up as Lu-177. The enrichment step has historically been dominated by Russian electromagnetic separators (calutrons), described as 100% European dependence on Russia for this specific material.

• ytterbium-176 / yb-176
• one in 5,000
• calutrons
• 100% european dependence

It needs a licensed hot lab with shielded space, a dose calibrator, syringe shields and pumps, and a decay-storage area for waste, plus a decay-in-storage process for low-level radioactive waste under 10 CFR 35.92 and shielded 'hot' toilets for patients who have received a therapeutic dose -- a UK readiness review lists these alongside licensing, imaging, treatment planning and follow-up as mandatory steps.

• hot lab
• dose calibrator
• decay-in-storage / decay-storage
• 10 cfr 35.92
• 'hot' toilets

The evidence is contested: a 2019 JNM editorial estimated only about 1,200 board-certified US nuclear medicine physicians with 50-60 new diplomates entering annually, yet argued the existing and incoming workforce could meet projected demand of 150,000-200,000 radionuclide therapy cycles a year if radiologists and radiation oncologists trained under the alternate pathway are counted. The NRC's own ACMUI subcommittee concluded in 2018-2019 that there was 'no objective data to confirm an authorized user shortage.'

• 1,200
• 50-60
• no objective data
• 150,000-200,000

Pluvicto (177Lu-PSMA-617) is approved and almost always given at a fixed activity of 7.4 GBq every six weeks, and the 2023 EANM/SNMMI guideline confirms dosimetry is not mandatory for in-label use. EANM's own January 2025 position states that 'divergent opinion persists' because there is a lack of sufficiently robust evidence that personalising activity based on dosimetry provides tangible benefit, even though studies show the cycles needed to reach a kidney dose limit range from 2 to 10 across patients.

• 7.4 gbq
• divergent opinion persists / divergent opinion
• 2 to 10
• fixed activity / fixed-activity

New diagnostic radiopharmaceuticals typically get two to three years of transitional 'pass-through' status during which their cost is separately and fully reimbursed; once pass-through expires, additional payment can drop to zero, which the American College of Radiology cites as the reason amyloid PET imaging has had persistently limited availability. CMS's CY2025 HOPPS rule created a new middle tier paying Mean Unit Cost for products above a $630 per-day threshold, with twenty-six products qualifying for 2025.

• pass-through
• drop to zero
• $630
• mean unit cost

Because radioactive decay cannot be paused, every shipment is calibrated to an activity that must hold at a specific date and time; molybdenum-99, with its 66-hour half-life, loses about 22% of its activity to a single day's transport delay, and shipments also travel as Class 7 dangerous goods, which restricts which carriers will accept them. A missed delivery window is not simply a late shipment -- the product is unusable and cannot be replaced from any stockpile.

• 22%
• 66-hour
• cannot be replaced
• class 7

Legacy Ac-225 comes from milking thorium-229 cow generators at only four sites worldwide, yielding about 63 GBq a year. TerraPower Isotopes is building a Philadelphia facility intended to raise supply twenty-fold from thorium-229 recovered from a legacy uranium-233 stockpile, IONETIX opened a dedicated Alpha Isotope Manufacturing facility in Lansing, Michigan and reported first Ac-225 production there in June 2024 using cyclotron irradiation, and NorthStar Medical Radioisotopes brought an accelerator-based Ac-225 production facility online in 2024 to 2025 -- all shifting from thorium-229 decay toward accelerator irradiation of radium-226 or thorium-232 targets.

• 63 gbq
• twenty-fold
• lansing, michigan / alpha isotope manufacturing
• radium-226

Small molecules such as kinase inhibitors are cleared by the liver and kidneys within hours to a day, so they must be taken daily, while a radioactive drug's own physical half-life sets how long it keeps irradiating the tumour: lutetium-177 has a physical half-life of 6.6 days, which is part of why it is only given every few weeks rather than daily.

• hours to a day
• daily
• 6.6 days
• physical half-life

Specific activity is the activity of a radionuclide divided by the total mass of the labelled compound present, expressed as GBq/mg, and no labelling reaction is perfectly efficient, so every batch contains some non-radioactive 'cold' copies of the same targeting molecule. Because the cold carrier competes with the radiolabelled molecule for a limited number of receptor binding sites, low specific activity can reduce tumour uptake per unit of injected mass, a stake described as receptor saturation.

• specific activity
• cold
• receptor saturation / competes
• gbq/mg

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, but travel only 50 to 100 micrometres, so they lack that reach and instead cause oxygen-independent DNA breaks in the immediate cells rather than crossfiring across a bulky mass.

• crossfire
• 100 kev per micrometre
• 1 to 10 mm
• 50 to 100 micrometres

A theranostic pair is a diagnostic and a therapeutic radiopharmaceutical that share the same targeting molecule, so the diagnostic scan predicts where the therapy will localise and deliver dose. The current dominant example for prostate cancer is 68Ga/177Lu-PSMA-617, which pairs gallium-68 PET imaging with lutetium-177 therapy.

• theranostic pair
• 68ga
• 177lu
• psma-617

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 of it.

• standardised uptake value
• suv
• suvmax
• normalised to the injected dose

Biochemical recurrence is a PSA of 0.2 ng/mL or more after prostatectomy, usually years before anything is visible on a scan, and PSMA PET can now find the recurrent disease at very low PSA levels in most men. A lesion scored PSMA-RADS 3A falls in the equivocal 3A/3B/3C/3D band, warranting further work-up such as biopsy or 3-6 month follow-up imaging rather than being treated as confirmed cancer.

• biochemical recurrence
• 0.2 ng/ml
• psma-rads
• equivocal
• further work-up

Not necessarily. A Deauville score of 4 means uptake moderately higher than liver, and under the Lugano classification this counts as a partial metabolic response if uptake has fallen from baseline. It is only called progressive metabolic disease if uptake is increasing or there are new FDG-avid lesions, and 'no metabolic response' if score 4 or 5 uptake is simply unchanged.

• deauville
• moderately higher than liver
• partial metabolic response
• progressive metabolic disease

Under USP General Chapter <825>, a compounded radiopharmaceutical must undergo a quality assessment appropriate to the preparation, which can include radionuclidic purity, radiochemical purity, chemical purity, pH and physical appearance, plus sterility and endotoxin testing for injectables made from non-sterile components. Radiochemical purity for 177Lu-labelled therapeutics typically starts near 98% at the end of synthesis and must be tracked through the product's beyond-use date because it falls over time from radiolysis.

• usp general chapter <825>
• radiochemical purity
• radionuclidic purity
• beyond-use date
• 98%

Only an Authorized User - a physician who has met US Nuclear Regulatory Commission training-and-experience requirements under 10 CFR Part 35 and is named on the clinic's licence - may prescribe or administer the radioactive drug, following a written directive for therapies such as lutetium-177 or iodine-131. Staff exposure is separately governed by ALARA, which requires every reasonable effort to keep doses as far below the regulatory limits as is practical, using shielding, distance and time.

• authorized user
• 10 cfr part 35
• alara
• shielding

The becquerel (Bq) measures activity, the rate of radioactive decay, with one Bq equal to one nuclear disintegration per second; the older unit is the curie, defined as 1 Ci = 3.7 x 10^10 Bq. The gray (Gy) measures absorbed dose, the energy actually deposited in tissue, defined as 1 Gy = 1 J/kg, and is the quantity that determines whether a tumour or organ is treated or harmed. The sievert (Sv) is used for equivalent and effective dose in radiation protection, applying a biological weighting on top of absorbed dose, and is not used to prescribe or evaluate radiopharmaceutical therapy.

• becquerel
• 3.7 x 10^10
• gray
• sievert

Bone-avid Tc-99m bisphosphonate tracers such as pyrophosphate bind ATTR amyloid deposits in the heart. Gillmore et al. (2016, JAMA Cardiology, n=1,217) showed that grade 2-3 uptake, combined with the absence of a monoclonal protein, had 100% specificity and positive predictive value for ATTR-CM, avoiding endomyocardial biopsy in most patients, though SPECT or SPECT/CT confirmation of myocardial uptake is now required.

• gillmore
• 100% / 100 percent
• grade 2-3 / grade 2 / grade 3
• spect

Since 2024, fluorine-18 flurpiridaz PET myocardial perfusion imaging adds absolute myocardial blood flow quantification in mL/min/g and a lower radiation dose per study compared with rubidium-82 or nitrogen-13 ammonia. Its longer half-life also permits exercise stress PET, which was previously impractical with short-lived PET tracers.

• flurpiridaz
• ml/min/g
• exercise stress pet / exercise stress
• 2024

Idiopathic Parkinson's disease and the atypical parkinsonisms multiple system atrophy and progressive supranuclear palsy all share loss of dopaminergic nerve terminals in the striatum, so an abnormal DAT SPECT with reduced or absent striatal uptake supports a parkinsonian syndrome but, as the drug label makes explicit, cannot distinguish Parkinson's disease from multiple system atrophy or progressive supranuclear palsy, since all three produce similar transporter loss.

• multiple system atrophy / msa
• progressive supranuclear palsy / psp
• drug label
• striatal uptake / striatum

The 2024 Alzheimer's Association revised criteria treat a positive amyloid biomarker on PET or CSF as a 'Core 1' biomarker, sufficient together with clinical context to support a biological diagnosis of Alzheimer's disease, with tau PET (flortaucipir) as a 'Core 2' biomarker used to stage disease severity. A negative amyloid scan is strong evidence against AD as the cause of cognitive impairment.

• core 1
• core 2
• 2024
• tau pet / flortaucipir

The EANM procedural guideline specifies three imaging time points after reinjecting Tc-99m-HMPAO-labelled autologous leukocytes: roughly 30-60 minutes, 2-4 hours, and 20-24 hours, because the diagnostic sign is an increase in uptake over time rather than its mere presence; a decrease or stable pattern between the delayed and late images points to a sterile process instead. Reported sensitivity for periprosthetic joint infection is around 86-93% and specificity 94-100%.

• 30-60 minutes
• 20-24 hours
• 86-93
• hmpao

Work-up establishes that the gland is actually iodine-avid: thyroid function tests and a radioiodine uptake measurement or Tc-99m pertechnetate scan distinguish Graves' disease and toxic nodules, which show high uptake, from destructive thyroiditis or factitious thyrotoxicosis, which show low uptake and will not respond to I-131. A serum TSH above about 30 mIU/mL maximises uptake, and dosing targets roughly 2.96-7.4 MBq per gram of thyroid tissue.

• 30 miu
• 2.96-7.4 / 2.96
• high uptake
• i-131 / iodine-131

HiLo and ESTIMABL2 showed that low-risk patients gain nothing from radioactive iodine, so it is reserved for intermediate and high-risk patients after surgery; active surveillance is accepted for microcarcinomas and lobectomy suffices for many low-risk cases.

• hilo
• estimabl2
• low-risk / low risk
• radioactive iodine / i-131

SDHx-related tumours fall in cluster 1 (SDHx, VHL, FH, EPAS1), which are pseudohypoxic, often extra-adrenal and multiple, and express somatostatin receptors strongly, so 68Ga-DOTATATE PET is the preferred whole-body scan for this group, unlike cluster 2 (RET, NF1, MAX, TMEM127) tumours, which are kinase-driven and adrenergic.

• 68ga-dotatate / 68ga / gallium-68
• cluster 1
• somatostatin receptor / somatostatin receptors
• sdhx

ANBL0032 randomised 226 children after transplant to isotretinoin alone or with the anti-GD2 antibody dinutuximab (ch14.18), GM-CSF and interleukin-2: two-year event-free survival was 66% versus 46%, and overall survival 86% versus 75%; dinutuximab was approved in March 2015.

• dinutuximab
• 66 percent / 66%
• 86 percent / 86%
• march 2015

No. Strontium-89, samarium-153 and radium-223 all concentrate in osteoblastic bone lesions to relieve pain over one to a few weeks, but only radium-223, an alpha-emitter, is approved specifically for castration-resistant prostate cancer with symptomatic bone metastases and no visceral disease, and it prolongs overall survival, per the ALSYMPCA trial, unlike the older beta emitters which only relieve pain.

• radium-223 / 223ra
• alsympca
• overall survival
• strontium-89 / samarium-153

Global actinium-225 production is only about 63 GBq (1.7 Ci) per year, enough for roughly 100-200 patients annually, and lutetium-177 production is separately constrained by the need for enriched ytterbium-176, historically sourced mainly from Russia. Both bottlenecks are on the supply side rather than the biology, which is why the roadmap's emerging step of bringing 225Ac and 212Pb into trials depends on isotope supply catching up.

• 63 gbq / 1.7 ci
• 100-200 patients
• ytterbium-176 / yb-176
• russia

PSMA PET/CT is required to confirm your tumour actually expresses PSMA before PSMA-targeted radioligand therapy can be given: the 2026 NCCN guidelines and the joint EANM/SNMMI guideline require PSMA PET to select patients for PSMA-targeted radioligand therapy, because a meaningful fraction of patients are PSMA-negative or discordant on biopsy. The scan is the diagnostic half of the same theranostic pair that Pluvicto belongs to.

• select patients for psma-targeted radioligand therapy
• psma-negative / discordant
• nccn
• pluvicto

The VISION trial fixed dosing at 7.4 GBq every six weeks for up to six cycles regardless of individual kidney or tumour dose, but a University of Wisconsin series found 15 of 19 patients could have safely received a seventh cycle and 18 of 19 an additional cycle under a 24 Gy kidney and 20 Gy salivary gland threshold, and the LUMEN and LUTADOSE studies showed tumour-absorbed dose after the first cycle predicts progression-free survival. Trials such as FLEX-MRT are now testing a flexible, response-guided schedule directly against the fixed regimen.

• 7.4 gbq
• 24 gy
• lumen / lutadose
• flex-mrt

The roadmap has already gone from OctreoScan (1994) through 68Ga-DOTATATE PET (2016) to 177Lu-DOTATATE (Lutathera, 2018), with NETTER-2 extending it to first-line grade 2/3 disease and to adolescents in 2024. The current frontier is alpha-emitting versions of the same pharmacophore, such as 225Ac-DOTATATE (RYZ101), aimed at patients whose disease progresses after beta-emitting PRRT.

• octreoscan
• netter-2
• 225ac-dotatate / ryz101
• progresses after beta-emitting prrt / beta-emitting prrt

Most radioligand strategies need a tumour-specific target such as PSMA or SSTR2, which not every cancer expresses, so this idea instead targets the cancer-associated fibroblasts that almost all solid tumours share, irrespective of tumour-cell genotype, giving crossfire into adjacent tumour cells. It is aimed at the bottleneck of cold tumours and the immunosuppressive microenvironment, at a stage where FAPI PET still does not have the guideline weight of PSMA or SSTR PET.

• cancer-associated fibroblasts
• irrespective of tumour-cell genotype / tumour-cell genotype
• cold tumours and the immunosuppressive microenvironment / cold tumours
• guideline weight

Programmes such as 225Ac-PSMA-I&T (FPI-2265) in the AlphaBreak programme and 225Ac-PSMA-617 (AAA817, Novartis) in a phase 3 programme are being trialled largely in patients who progressed on or are refractory to lutetium-177 therapy, but actinium-225 is scarce and the field still lacks randomised phase 3 evidence for any alpha-PSMA agent. A proposed fix is to fund alternative alpha emitters such as lead-212 and terbium-149 so the field is not dependent on a single supply chain.

• fpi-2265 / alphabreak
• aaa817
• lacks randomised phase 3 evidence
• lead-212 / terbium-149

Global actinium-225 production is only about 63 GBq (1.7 Ci) a year, enough for roughly 100-200 patients annually, while estimated clinical and trial demand is far higher, so alpha-PSMA agents remain in phase 1/2 development, mostly for patients who have already progressed on or are refractory to lutetium-177 therapy, rather than being available as routine care.

• 63 gbq / 1.7 ci
• 100-200 patients
• phase 1/2
• refractory to lutetium-177

One proposal recovers legacy radium-226 from disused brachytherapy sources and uranium mill tailings as cyclotron feedstock; another proposes regional cyclotron or linac hubs paired with a harmonised pharmacopoeia monograph settling the actinium-227 impurity limit that proton irradiation of radium-226 produces; a third scales up accelerator production via thorium-232 spallation, which Brookhaven showed in 2021 could generate about 60% of the entire annual thorium-229-derived supply in a single 12-day campaign. They target feedstock recovery, regulatory harmonisation and accelerator scale-up respectively.

• brachytherapy sources / uranium mill tailings
• actinium-227
• 60% of the entire annual
• spallation

The current constraint is enriched ytterbium-176 target material for no-carrier-added Lu-177, historically sourced mainly from Russia, with demand rising sharply since Pluvicto and Lutathera. New capacity is being built to close the gap: Canada's Darlington reactor began isotope production runs (Mo-99, Lu-177, Y-90) from 2025, and SHINE Technologies' Chrysalis facility is already producing Lu-177 while targeting over 75% of US Mo-99 demand.

• ytterbium-176 / yb-176
• darlington
• shine
• 75%

Because it compares two maps of the same lungs. Air is mapped with an inhaled agent such as Technegas, and blood flow with injected Tc-99m macroaggregated albumin particles that lodge in the pulmonary capillaries. A clot shows as a segment that is ventilated but not perfused.

• technegas
• macroaggregated albumin / maa
• mismatch / ventilated but not perfused
• inhaled
• perfusion

It is technetium encapsulated in carbon, made by flash-heating dried Tc-99m pertechnetate in a graphite crucible at about 2,700 C in argon. The particles are nanometre-scale, under 500 nm aerodynamic diameter, so they travel with inspired air to the lung periphery instead of impacting in the central airways the way a wet aerosol such as Tc-99m DTPA does, which is what produces hot spots in obstructive disease.

• 2,700 c / carbon crucible / graphite crucible
• 500 nm / nanoparticle
• periphery / lung periphery
• dtpa / central airways / impact

Each particle works by physically occluding a pulmonary arteriole or capillary, so the safety margin comes from how few of them are given relative to the capillary bed: 200,000 to 700,000 particles for an adult, about 350,000 recommended, down to 10,000 to 50,000 for a neonate. It is contraindicated in severe pulmonary hypertension, where deaths have been reported.

• 200,000 to 700,000 / 350,000
• 10,000 to 50,000 / neonate
• capillar / arteriole
• pulmonary hypertension

Tc-99m MAA injected into the hepatic artery, imaged to estimate the lung shunt fraction, because hepatopulmonary shunting can deliver enough dose to the lungs to cause radiation pneumonitis. The usual constraint is a lung mean dose of 30 Gy from one treatment or 50 Gy cumulative, and a shunt above 20% has traditionally ruled out resin microspheres.

• lung shunt fraction / shunt
• hepatic artery
• 30 gy / 50 gy
• radiation pneumonitis

Yes, one. Perspective Therapeutics' lead-212 PSV359 targets FAP-alpha on cancer-associated fibroblasts; in September 2026 its phase 1/2 trial NCT06710756 was amended with Merck to add cohorts combining it with pembrolizumab in FAP-alpha-positive non-small cell lung cancer and colorectal cancer.

• psv359
• fap-alpha / fibroblast activation protein
• pembrolizumab
• non-small cell lung cancer / nsclc

The FDA approved it on 29 September 2023 under NDA 022335, held by Cyclomedica Australia, after the CYC-009 phase 3 study comparing it with xenon-133 planar imaging. It was already sold in 65 countries with more than 5 million procedures performed; US revenue-generating sites went from 35 in June 2025 to 83 by August 2026.

• 29 september 2023 / nda 022335
• xenon-133
• 65 countries / 5 million
• cyclomedica / cyclopharm

Its parent rubidium-81 is cyclotron-made and lasts about 4.6 hours, so a generator has to be delivered daily from a nearby cyclotron. That logistics, not the physics, confined it to a few countries; the only US product was withdrawn effective 7 December 2007. The gas itself is excellent: a 13-second half-life and a 190 keV photon well separated from technetium's 140 keV, which lets ventilation and perfusion be acquired simultaneously.

• 4.6 hours / rubidium-81
• cyclotron
• 13-second / 190 kev
• withdrawn / 7 december 2007

A quantitative perfusion scan gives the fraction of total perfusion belonging to the lung to be removed, and predicted postoperative FEV1 is preoperative FEV1 times one minus that fraction. The ACCP guideline needs no further testing if predicted postoperative FEV1 and DLCO both exceed 60% of predicted, a low-technology exercise test if either is below 60% with both above 30%, and formal cardiopulmonary exercise testing if either is below 30%. Before a lobectomy, segment counting predicts about as well, so the scan is reserved for pneumonectomy and borderline function.

• fraction of total perfusion
• 60%
• 30%
• segment counting
• pneumonectomy

Using the same targeting molecule for a diagnostic scan and a treatment: PSMA PET shows where prostate cancer is, and 177Lu-PSMA-617 (Pluvicto) delivers radiation to the same target.

• same / pair / diagnos
• psma
• pet / scan / imag
• pluvicto / lutetium / 177lu / radioligand

177Lu-PSMA-617 plus standard care improved overall survival, 15.3 versus 11.3 months, in PSMA-positive metastatic castration-resistant prostate cancer after an androgen receptor pathway inhibitor and a taxane; it met both primary endpoints, overall and radiographic progression-free survival.

• pluvicto / 177lu / lutetium / psma-617
• overall survival / os / 15.3 / 11.3
• castration-resistant / mcrpc
• radiographic progression-free survival / both primary endpoints

Alpha particles (actinium-225) deposit far more energy over 50-100 micrometres, causing clustered double-strand breaks independent of oxygen and cell cycle, so beta-resistant, hypoxic, or small-volume disease can still be killed; retrospective series show PSA responses in about half after 177Lu failure. Supply of Ac-225 and salivary toxicity are the limits.

• alpha
• actinium / 225ac / ac-225
• double-strand / energy / let / clustered
• supply / salivary / xerostomia / toxicity

177Lu emits beta particles (range 1-10 mm, crossfire helps bulky heterogeneous tumours, marrow toxicity, 6.65-day half-life); 225Ac emits alpha particles (range 50-100 micrometres, very high energy, oxygen-independent clustered DNA damage, good for micrometastases, daughter redistribution and supply constraints).

• beta
• alpha
• range / mm / micromet
• supply / daughter / marrow / toxicity

It is made in tiny quantities from a legacy thorium-229 stockpile recovered from uranium-233, or from accelerators. TerraPower Isotopes is building a Philadelphia facility intended to raise supply twenty-fold and ITM is investing in actinium-225 supply, so phase 3 alpha trials and any launch are gated by production, which the corpus calls the binding constraint.

• thorium / stockpile / accelerator / produc
• terrapower
• twenty-fold / 20-fold / philadelphia
• trials / launch / gate / bottleneck / constraint

Heidelberg (University Hospital, DKFZ/NCT; Haberkorn, Giesel, Kratochwil), which also ran the first-in-human 225Ac-PSMA therapy.

• heidelberg
• dkfz / nct / university hospital
• haberkorn / giesel / kratochwil / germany
• psma / actinium / 225ac

Not an approved one. Tarlatamab, a DLL3-directed bispecific T-cell engager, was given accelerated approval on 16 May 2024 and traditional approval on 19 November 2025, but selection still rests on immunohistochemistry from one biopsy. The only imaging agent with human data is the zirconium-89 antibody 89Zr-DFO-SC16.56, reported in Lancet Oncology in 2024 in 18 patients, with uptake congruent with DLL3 immunohistochemistry in 15 of 16 patients with evaluable tissue.

• tarlatamab
• 89zr-dfo-sc16.56 / zirconium-89
• immunohistochemistry
• 18 patients / 15 of 16

Because the existing one is cleared the wrong way. The bicyclic peptide 68Ga-N188 from Peking University has first-in-human data in 14 patients and a 62-patient head-to-head against FDG, but it is excreted in urine, which a 2025 review says poses challenges for in-situ bladder cancer detection because of high background activity in the urinary tract. The opportunity is a Nectin-4 ligand cleared hepatobiliary rather than renally, so the bladder and pelvic nodes can be read.

• 68ga-n188
• excreted in urine / urinary tract / background activity
• hepatobiliary
• enfortumab vedotin

Not a specific one. Arcitumomab, the anti-CEA antibody fragment approved for exactly this problem, was withdrawn from the US and EU markets in 2005 and nothing has replaced it, so teams use FDG PET/CT off-label; in one referred series it found recurrence in 56 of 88 patients with raised CEA and negative conventional imaging. Tumour-informed ctDNA now detects recurrence about 5.9 months before imaging does, which creates more patients needing localisation, not fewer.

• arcitumomab
• 2005
• 56 of 88 / fdg pet/ct
• ctdna / 5.9 months

Because measuring HER3 has not predicted who benefits. Three antibody tracers were built and all three belong to drug programmes that stalled or were discontinued, and patritumab deruxtecan's own biomarker analyses report no relationship between efficacy and HER3 protein expression by immunohistochemistry. One published tracer study could determine no correlation between tumour uptake and ex-vivo immunohistochemistry, and the drug's BLA was withdrawn in May 2025 after HERTHENA-Lung02 missed overall survival.

• patritumab
• no relationship between efficacy / no correlation
• herthena-lung02 / withdrawn
• three antibody pet tracers / discontinued / stalled

Against whole-tumour-section truth, a single representative biopsy gave 58.8% sensitivity for CLDN18.2, rising to 76.5% with six to eight biopsies, and 18% of tumours were discordant between the primary and the matched nodal metastasis. A multi-laboratory ring trial found a 12% false-negative rate. That matters because zolbetuximab and a CLDN18.2 CAR-T are both given only to patients whose tissue tests positive.

• 58.8%
• 76.5% / six to eight biopsies
• 18% / discordant
• 12% / ring trial
• zolbetuximab

No test is required for either sacituzumab govitecan or datopotamab deruxtecan, but the level does appear to matter: in the ASCENT biomarker analysis, high TROP2 expression gave an objective response rate of 44% against 22% in the low group, with progression-free survival of 6.9 against 2.7 months. The reason there is no test is that the assays disagree, with only fair-to-moderate concordance between three immunohistochemistry assays and no validated plasma assay.

• sacituzumab govitecan
• 44% / 22%
• 6.9 / 2.7 months
• no validated plasma / concordance

In the phase 3 ZIRCON trial, 300 patients were dosed and 284 were evaluable, giving sensitivity of 85.5% and specificity of 87.0% for clear cell renal cell carcinoma with no safety signals. It is still not approved anywhere: the FDA issued a complete response letter on chemistry, manufacturing and controls rather than on efficacy or safety. The problem it addresses is that between 12.8% and 40% of resected small renal masses turn out to be benign.

• zircon
• 85.5%
• 87.0%
• complete response letter
• benign

Not yet proven at scale, but close. 68Ga-PentixaFor holds EMA PRIME status and FDA Fast Track designation, with a phase 3 called PANDA planned at approximately 270 patients. In a 100-patient prospective study, PET/CT agreed with adrenal vein sampling in 90% of patients against 54% for conventional CT. The reason it matters is access: primary aldosteronism accounts for 5 to 14% of all hypertension and fewer than 1% of patients are identified and fully investigated.

• pentixafor
• prime / fast track
• 270 patients / panda
• 90% / 54%
• fewer than 1%

Not in Parkinson's disease itself. The most advanced tracer, [18F]ACI-12589, was studied in 42 participants and separates multiple system atrophy from controls and from other neurodegenerative disorders, but shows limited binding in Parkinson's disease. A cerebrospinal fluid seed amplification assay already identifies Parkinson's with 87.7% sensitivity and 96.3% specificity, though it cannot say where in the brain the pathology is.

• aci-12589
• multiple system atrophy
• limited binding
• 87.7% / 96.3%

A Cochrane review found the median pre-test probability of unresectable disease after CT was 41.4%, so 41 of 100 patients who looked resectable on CT were unresectable at laparotomy. FAPI PET detects more: a pancreatic-specific meta-analysis of 7 studies and 322 patients gives pooled sensitivity of 0.99 against 0.84 for FDG, and 18F-FAPI-04 upgraded the TNM stage in 14 of 62 patients. What no trial has yet shown is that FAPI-based selection reduces the non-curative laparotomy rate.

• 41.4%
• 0.99 / 0.84
• 14 patients / upgraded the tnm stage
• non-curative laparotomy / has yet reported

Because FDG needs the patient's myocardium suppressed by a strict diet and imperfect suppression produces false positives on which immunosuppression is then started, while the histological reference standard is worse: endomyocardial biopsy sensitivity is roughly 20 to 30%, and there is no reliable serum biomarker. Somatostatin receptor tracers need no dietary preparation; in 11 patients, 68Ga-DOTATATE gave 91% patient-level concordance with FDG but only 77.1% segment-level agreement.

• dietary / suppression
• 20 to 30% / endomyocardial biopsy
• 91%
• 77.1%

Mostly in China, aimed at glypican-3, which is overexpressed in 70 to 80% of hepatocellular carcinomas and effectively absent from normal liver. The problem is that 31% of LR-3 and 64% of LR-4 LI-RADS observations prove to be cancer. The most mature single dataset is Western, a 24-patient first-in-human series of [68Ga]Ga-RAYZ-8009, but the deepest programme is 68Ga-XH06 at Wuhan Union Hospital under NCT06383520, with a registered 150-patient head-to-head against enhanced MRI.

• 70 to 80%
• lr-3 / lr-4
• rayz-8009
• xh06 / nct06383520