{"entity":{"id":"dosimetry-roadmap","kind":"roadmap","name":"Dosimetry roadmap: MIRD schema → fixed dosing → personalised, image-based dose","aka":[],"tldr":"Working out how much radiation a treatment actually delivers to a tumour and to healthy organs, rather than just giving everyone the same fixed amount, could let doctors treat some patients more and some less. The tools to do this patient by patient exist and are used in some specialist centres, but most approved radioligand therapies are still given at one fixed dose to everyone.","summary":"Internal radiation dosimetry has a formal history: the Society of Nuclear Medicine's Medical Internal Radiation Dose (MIRD) Committee was formed in 1965, and its 1968 MIRD Pamphlet No. 1 (Loevinger and Berman) introduced the absorbed-fraction and S-value formalism that still underlies software such as OLINDA. For decades this framework was applied mainly to diagnostic radiopharmaceutical dose estimates rather than to individualising therapy.\n\nPersonalised, image-based dosimetry for peptide receptor radionuclide therapy (PRRT) was developed and tested prospectively from the early 2010s, principally by Swedish groups: Sandström et al. and Garske-Román et al. at Uppsala, and Sundlöv et al. at Lund, used SPECT/CT-based kidney dosimetry to vary the number of 177Lu-DOTATATE cycles per patient up to a fixed renal biologically effective dose (27 Gy, with a 40 Gy option in low-risk patients) rather than a fixed four-cycle course. Despite this evidence base, the pivotal trials that led to approval, NETTER-1 for Lutathera (FDA, January 2018) and VISION for Pluvicto (FDA, March 2022), used fixed activities and a fixed number of cycles, and the resulting labels do not require patient-specific dosimetry for in-label use.\n\nThe current step is guideline consolidation: the joint EANM/SNMMI procedure guideline for 177Lu-PSMA radioligand therapy (2023) states plainly that fixed dosing was how the drug was approved and that dosimetry is not mandatory in-label, while EANM's 2022 dosimetry-committee recommendations and its 2024 guidance for first-in-human studies push in the opposite direction, calling for patient-specific absorbed-dose calculation as standard practice, especially early in a new drug's development. The emerging and speculative steps are quantitative SPECT/CT and total-body PET made fast and automated enough for routine clinical dosimetry, and trials that prospectively randomise dosimetry-guided dosing against the fixed-activity standard of care.","asOf":"2026-09-22","links":[{"label":"From the MIRD Committee: history and founding, 1965 (J Nucl Med)","url":"https://jnm.snmjournals.org/content/jnumed/50/2/25N.full.pdf"},{"label":"Sundlöv et al., individualised 177Lu-DOTATATE treatment based on kidney dosimetry (Eur J Nucl Med Mol Imaging 2017)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5506097/"},{"label":"Joint EANM/SNMMI procedure guideline for 177Lu-PSMA-RLT (2023)","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10317889/"}],"tags":[],"related":["lu-177"],"indications":[],"sections":[],"technologies":["radioligand-dosimetry","in-vivo-dosimetry","spect-ct","total-body-pet-screening"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["dosimetry","gray-unit"],"trials":["netter-1","vision"],"people":["clemens-kratochwil","ken-herrmann"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"steps":[{"era":"1965-1968","title":"The MIRD schema","description":"The Society of Nuclear Medicine forms the Medical Internal Radiation Dose (MIRD) Committee in 1965. Its 1968 MIRD Pamphlet No. 1 (Loevinger and Berman) introduces the absorbed-fraction and S-value formalism for internal dosimetry, replacing older exposure-based (roentgen) methods and forming the basis of modern dosimetry software.","refs":["dosimetry"],"status":"historic"},{"era":"2012-2017","title":"Prospective personalised PRRT dosimetry trials","description":"Swedish groups develop and prospectively test image-based, patient-specific PRRT dosing: Sandström and Garske-Román's Uppsala cohort of 200 patients caps 177Lu-DOTATATE at a 23 Gy renal dose rather than a fixed cycle count, and Sundlöv's Lund phase 2 trial (NCT01456078) individualises cycles up to a 27 Gy renal biologically effective dose, reporting the approach as feasible and safe.","refs":["prrt","sstr2","idea-net-dosimetry-prrt"],"status":"historic"},{"era":"2018-2022","title":"Fixed-activity dosing wins regulatory approval","description":"Despite the personalised-dosimetry evidence base, the pivotal trials that gained approval both use fixed dosing: NETTER-1 (Lutathera, FDA January 2018) gives 7.4 GBq every 8 weeks for 4 doses, and VISION (Pluvicto, FDA March 2022) gives 7.4 GBq every 6 weeks for up to 6 doses, with dosimetry collected in a VISION sub-study of only 29 patients rather than used to set the dose.","refs":["netter-1","vision","lutathera","pluvicto"],"status":"historic"},{"era":"2022-2024","title":"Guidelines diverge on whether dosimetry should be mandatory","description":"EANM's dosimetry committee publishes recommendations for 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands (2022). The joint EANM/SNMMI procedure guideline for 177Lu-PSMA radioligand therapy (2023) states that '[177Lu]Lu-PSMA-617 was approved using fixed standard treatment activities, and patient individual dosimetry is not mandatory for in-label use', while acknowledging significant inter-patient variability. EANM's 2024 guidance document for first-in-human studies and early-phase trials calls for patient-specific absorbed-dose calculation as standard in that earlier setting.","refs":["radioligand-dosimetry","in-vivo-dosimetry"],"status":"current"},{"era":"2024-2028","title":"Emerging: faster quantitative imaging for routine dosimetry","description":"Work continues on shortening and simplifying SPECT/CT-based kidney and bone-marrow dosimetry protocols (for example, reducing the number of post-therapy imaging time points needed) and on total-body PET platforms whose sensitivity could make same-day, whole-body quantitative dosimetry practical outside specialist academic centres.","refs":["spect-ct","total-body-pet-screening","idea-total-body-pet-dosimetry"],"status":"emerging"},{"era":"2028+","title":"Speculative: dosimetry-personalised dosing as standard of care","description":"If ongoing and future randomised trials show that dosimetry-guided cycle number or activity improves outcomes or reduces toxicity compared with fixed dosing, regulators could require or incentivise individualised dosing for new and existing radioligand therapies rather than leaving it as an optional academic practice.","refs":["idea-net-dosimetry-prrt"],"status":"speculative"}],"watch":[{"item":"Joint EANM/SNMMI procedure guideline for 177Lu-PSMA-RLT, next revision","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10317889/","refs":["radioligand-dosimetry"]}]},"route":"/roadmaps/dosimetry-roadmap/","neighbours":{"isotope":[{"id":"lu-177","kind":"isotope","name":"Lutetium-177","route":"/isotopes/lu-177/"}],"technology":[{"id":"in-vivo-dosimetry","kind":"technology","name":"In vivo dosimetry and patient-specific quality assurance","route":"/technologies/in-vivo-dosimetry/"},{"id":"prrt","kind":"technology","name":"Peptide receptor radionuclide therapy (PRRT)","route":"/technologies/prrt/"},{"id":"radioligand-dosimetry","kind":"technology","name":"Radioligand dosimetry","route":"/technologies/radioligand-dosimetry/"},{"id":"spect-ct","kind":"technology","name":"SPECT/CT","route":"/technologies/spect-ct/"},{"id":"total-body-pet-screening","kind":"technology","name":"Total-body PET for screening and ultra-low-dose imaging","route":"/technologies/total-body-pet-screening/"}],"term":[{"id":"dosimetry","kind":"term","name":"Dosimetry","route":"/terms/dosimetry/"},{"id":"gray-unit","kind":"term","name":"Gray unit (Gy)","route":"/terms/gray-unit/"}],"trial":[{"id":"netter-1","kind":"trial","name":"NETTER-1","route":"/trials/netter-1/"},{"id":"vision","kind":"trial","name":"VISION","route":"/trials/vision/"}],"person":[{"id":"clemens-kratochwil","kind":"person","name":"Clemens Kratochwil","route":"/people/clemens-kratochwil/"},{"id":"ken-herrmann","kind":"person","name":"Ken Herrmann","route":"/people/ken-herrmann/"}],"target":[{"id":"sstr2","kind":"target","name":"Somatostatin receptor 2","route":"/targets/sstr2/"}],"idea":[{"id":"idea-net-dosimetry-prrt","kind":"idea","name":"Dosimetry-personalised PRRT instead of four fixed cycles","route":"/ideas/idea-net-dosimetry-prrt/"},{"id":"idea-total-body-pet-dosimetry","kind":"idea","name":"Total-body PET for personalised radioligand dosing","route":"/ideas/idea-total-body-pet-dosimetry/"}],"drug":[{"id":"lutathera","kind":"drug","name":"Lutetium-177 dotatate","route":"/drugs/lutathera/"},{"id":"pluvicto","kind":"drug","name":"Lutetium-177 vipivotide tetraxetan","route":"/drugs/pluvicto/"}]}}