bottlenecksBottleneck

Dosimetry standardisation for radioligand therapy

Doctors give almost every patient the same fixed amount of radioactive drug, rather than measuring how much radiation each person's tumour and organs actually absorb and adjusting the dose. Personalising the dose might work better for some patients, but nobody has yet proven it clearly enough for it to become the standard of care.

177Lu-PSMA-617 (Pluvicto) is approved and almost always given at a fixed activity of 7.4 GBq every six weeks; the joint 2023 EANM/SNMMI procedure guideline confirms that patient-specific dosimetry is not mandatory for in-label use. Yet academic dosimetry studies show wide inter-patient variation: EANM Dosimetry Committee analyses report that the number of PRRT cycles needed to reach a preset kidney absorbed-dose limit ranges from 2 to 10 across patients, and the total activity required to hit that limit varies by a factor of roughly 1.5 for somatostatin-receptor therapy and by a factor of 3 for PSMA therapy.

The unresolved question is whether measuring and personalising that dose actually improves outcomes enough to justify the extra imaging burden. In its January 2025 reply to an EMA concept paper on clinical evaluation of therapeutic radiopharmaceuticals, EANM stated plainly that 'divergent opinion persists... the lack of sufficiently robust evidence demonstrating that personalizing administered activities based on dosimetry provides tangible benefits' means EANM does not hold a definitive position recommending dosimetry-guided over fixed-activity dosing. Methods themselves are only partly harmonised: the EANM Dosimetry Committee's 2022 recommendations for 177Lu-SSTR/PSMA dosimetry, and MIRD Pamphlet No. 26 for quantitative 177Lu SPECT, describe standard operating procedures, but implementation still varies by centre in imaging timepoints, segmentation method and software.

Alpha emitters add a further layer of difficulty: EANM's same 2025 submission flags that actinium-225's limited imaging potential on current nuclear-medicine cameras means image-based dosimetry approaches developed for beta emitters do not simply transfer across, and new strategies or technology are still needed.

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Scale of the problem

range 2–10 cycles

Number of PRRT cycles needed to reach a preset kidney dose limit, across patients

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~1.5-fold (SSTR therapy), ~3-fold (PSMA therapy)

Variation in total activity needed to reach a preset absorbed-dose limit

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7.4 GBq (200 mCi) every 6 weeks (±1 week), dosimetry not mandatory in-label

177Lu-PSMA-617 approved regimen: fixed activity per cycle

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Root causes

No large randomised trial has yet shown that dosimetry-guided individualised dosing improves survival or reduces toxicity compared with fixed-activity dosing.
Dosimetry protocols (imaging timepoints, organ/tumour segmentation, software) are not fully harmonised across centres, so results are not always directly comparable.
Multiple SPECT/CT imaging sessions over days add patient burden and resource use that many centres cannot absorb for every patient.
Alpha emitters such as actinium-225 are difficult to image directly with current nuclear medicine cameras, so beta-emitter dosimetry methods do not transfer straightforwardly.

Current efforts

EANM Dosimetry Committee recommendations (2022) for harmonised dosimetry of 177Lu-labelled somatostatin-receptor- and PSMA-targeting ligands.
Joint EANM/MIRD Pamphlet No. 26 on quantitative 177Lu SPECT methodology for dosimetry.
EANM's proposal, in its 2025 EMA consultation reply, for a unified pan-European database to pool dosimetric data across centres and generate the evidence base still missing.
EANM guidance document specifically for dosimetry in first-in-human and early-phase clinical trials of new radioligands.

Success criteria

A trial-validated, low-burden dosimetry protocol shown to improve outcomes or reduce toxicity versus fixed dosing, harmonised across centres and reimbursed as standard practice where it adds value.