Dosimetry
Dosimetry works out exactly how much radiation dose a patient's tumour and healthy organs actually receive, so treatment can in principle be tailored to the person rather than given as one fixed dose to everyone.
Overview
Most approved radioligand therapy today is given as a fixed activity on a fixed schedule — 7.4 GBq of 177Lu-PSMA-617 every six weeks for up to six cycles, or 7.4 GBq of 177Lu-DOTATATE every eight weeks for four cycles — regardless of how much radiation dose that delivers to an individual patient's tumour, kidneys or bone marrow. Reported organ doses vary widely between patients: EANM dosimetry committee data for 90Y-DOTATOC give roughly 1.7-2.8 Gy/GBq to the kidneys, compared with about 0.6-0.9 Gy/GBq for 177Lu-DOTATATE, and comparable heterogeneity is reported for PSMA ligands.
Personalised, dosimetry-guided dosing has clear proof of principle outside radioligand therapy: in the DOSISPHERE-01 trial of yttrium-90 radioembolisation for hepatocellular carcinoma, a personalised multi-compartment dosimetry approach (target ≥205 Gy to the tumour) produced a median overall survival of 26.6 months versus 10.7 months with standard single-compartment dosing (HR 0.42, Garin et al., Lancet Gastroenterol Hepatol 2021). Bringing that logic to radioligand therapy is technically harder because it needs serial SPECT/CT or blood sampling after each cycle, and pure beta-emitters like 90Y have no gamma emission for direct imaging.
The field has not reached consensus on whether this is worth mandating. EANM's 2025 response to the EMA's concept paper on clinical evaluation of therapeutic radiopharmaceuticals states plainly that "given the current lack of conclusive clinical evidence," it does not hold a definitive position on recommending extensive individual dosimetry, simplified approaches, or fixed-activity posology, and asks regulators not to mandate dose-planned prescribing until the evidence and harmonised methods exist. This is the single biggest open methodological question in the field: whether individualised dosimetry meaningfully improves outcomes enough to justify its cost and complexity in routine practice, versus in trials only.
Notes
top- EANM's own 2025 position is that it does not have enough conclusive clinical evidence to recommend mandatory individual dosimetry over fixed-activity dosing for radioligand therapy.
- DOSISPHERE-01 is the clearest randomised proof that personalised dosimetry changes outcomes, but it is a radioembolisation trial, not a radioligand-therapy trial; the same case has not yet been made with equivalent rigour for 177Lu-PSMA or 177Lu-DOTATATE.
- Pure beta-emitters without a useful gamma line (e.g. 90Y) cannot be imaged directly for dosimetry, which is a physical, not just logistical, constraint on personalising some regimens.