Activity prescription: fixed versus dosimetry-guided dosing

Activity prescription is the process of deciding how much radioactivity (in gigabecquerel or millicurie) to administer per cycle of a radiopharmaceutical therapy, and how many cycles to give. Two broad approaches are used. Fixed (empirical) activity prescription gives every eligible patient the same standard activity per cycle, as established in the pivotal trials: 177Lu-PSMA-617 (Pluvicto) is approved and administered as 7.4 GBq (200 mCi) every six weeks for up to six cycles, as tested in the VISION trial, and 177Lu-dotatate (Lutathera) as a fixed 7.4 GBq per cycle for four cycles, as tested in NETTER-1, with dose reductions on toxicity but no upward personalisation. Regulators have approved these regimens without requiring patient-specific dosimetry for in-label use.

Dosimetry-guided (personalised) activity prescription instead measures each patient's own absorbed dose to organs at risk (chiefly kidneys and, for PSMA agents, salivary glands, and bone marrow for both) from an early cycle, using serial quantitative imaging and the MIRD formalism, and then adjusts subsequent cycle activity, or the number of cycles, to approach an organ dose-tolerance threshold (commonly cited working limits are around 23 Gy cumulative to the kidneys and around 2 Gy to red marrow) rather than stopping at a fixed number of fixed-size doses. Reported mean absorbed doses per unit administered activity vary widely between patients (for example roughly 0.4-1.9 Gy/GBq to salivary glands and roughly 0.4-1.0 Gy/GBq to kidneys for 177Lu-PSMA agents), which is the empirical basis for the argument that a single fixed activity under- or over-treats a substantial fraction of patients.

Dosimetry-guided prescription is used selectively in academic centres and in some national protocols, and is an active area of clinical trial development (see the idea of dosimetry-personalised PRRT instead of four fixed cycles), but it is more resource-intensive, requiring multiple post-therapy scans, quantitative calibration and physicist time, and has not replaced fixed dosing as the regulatory standard for the approved indications.