Dosimetry roadmap: MIRD schema → fixed dosing → personalised, image-based dose
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.
Overview
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.
Personalised, 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.
The 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.
- 1965-1968historic
The MIRD schema
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.
- 2012-2017historic
Prospective personalised PRRT dosimetry trials
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.
- 2018-2022historic
Fixed-activity dosing wins regulatory approval
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.
- 2022-2024current
Guidelines diverge on whether dosimetry should be mandatory
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.
- 2024-2028emerging
Emerging: faster quantitative imaging for routine dosimetry
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.
- 2028+speculative
Speculative: dosimetry-personalised dosing as standard of care
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.
Probability ranges are named estimates that the claim is borne out on roughly a five-year horizon. They are meant to be argued with: propose a revision with your name and reasoning via a pull request to src/data/confidence.ts.
What to watch
Readouts, decisions and registry completion dates ahead. Each date is quoted from its source, not inferred; a missing date means no source states one.
- no date stated
Story
topThe MIRD schema
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.
Prospective personalised PRRT dosimetry trials
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.
A radioactive version of the hormone mimic used for the scan; it homes to neuroendocrine tumour cells and irradiates them from inside.
Somatostatin receptor 2 is a hormone receptor densely present on neuroendocrine tumours, and was the first theranostic target to reach routine care.
Measure the radiation each patient's tumour and kidneys actually absorb and adjust the number and size of doses, instead of giving everyone four identical cycles.
Fixed-activity dosing wins regulatory approval
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.
The trial that made radioligand therapy a standard: a radioactive drug homing to the somatostatin receptor held midgut neuroendocrine tumours in check far longer than high-dose octreotide, and it underpins Lutathera's approvals.
VISION was the trial that established radioligand therapy in prostate cancer.
Lutetium-177 dotatate was the first modern radioligand therapy (2018), for neuroendocrine tumours, and is now used in first line.
A radioactive drug that seeks out PSMA on prostate cancer cells; the best-selling radiopharmaceutical ever.
Guidelines diverge on whether dosimetry should be mandatory
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.
Measuring, from scans taken after each dose, how much radiation a radioligand actually delivers to the tumour and to kidneys and marrow, so treatment can be personalised.
Measuring the dose the patient actually receives, with detectors on the skin or the imaging panel behind them, to catch errors before they cause harm.
Emerging: faster quantitative imaging for routine dosimetry
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.
A gamma camera with a CT scanner bolted on, so a hot spot on a bone scan or a sentinel-node scan is pinned to the exact bone or lymph node, and the dose from a radioactive drug can be measured after treatment.
Scanners sensitive enough to image the whole body in seconds at a fraction of the radiation dose, which raises the question of whether healthy people should be scanned at all.
Ultra-sensitive whole-body scanners can measure exactly where a radioactive drug goes at tiny tracer doses, allowing each patient's therapeutic dose to be tailored.
Speculative: dosimetry-personalised dosing as standard of care
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.
Similar pages
not linked directly; found by shared links- TermFixed versus personalised (dosimetry-guided) dosing
Shares Gray unit (Gy), Dosimetry-personalised PRRT instead of four fixed cycles, Total-body PET for personalised radioligand dosing, Radioligand dosimetry.
- BottleneckDosimetry standardisation for radioligand therapy
Shares In vivo dosimetry and patient-specific quality assurance, Dosimetry-personalised PRRT instead of four fixed cycles, Total-body PET for personalised radioligand dosing, Radioligand dosimetry.
- Key paperEANM dosimetry committee recommendations for dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands
Shares Gray unit (Gy), Dosimetry, Radioligand dosimetry, Peptide receptor radionuclide therapy (PRRT).
- IdeaKidney-dosimetry-guided dosing as the default for PSMA radioligand therapy
Shares Dosimetry-personalised PRRT instead of four fixed cycles, VISION, Radioligand dosimetry, Lutetium-177 vipivotide tetraxetan.
- PersonDale L. Bailey
Shares In vivo dosimetry and patient-specific quality assurance, SPECT/CT, Radioligand dosimetry, Lutetium-177.
- PersonErik S. Mittra
Shares NETTER-1, Peptide receptor radionuclide therapy (PRRT), Lutetium-177 dotatate, Lutetium-177.
- BottleneckWrong doses
Shares Dosimetry-personalised PRRT instead of four fixed cycles, Total-body PET for personalised radioligand dosing, Dosimetry, Peptide receptor radionuclide therapy (PRRT).
- TermRenal protection with amino acid co-infusion
Shares Gray unit (Gy), Peptide receptor radionuclide therapy (PRRT), Lutetium-177 dotatate, Lutetium-177.