Kidney-dosimetry-guided dosing as the default for PSMA radioligand therapy

The label dosing for lutetium-177 vipivotide tetraxetan (Pluvicto) is a fixed 7.4 GBq every six weeks for up to six cycles, as tested in the VISION trial, regardless of how much radiation an individual patient's kidneys, salivary glands or tumours actually receive. Dosimetry studies show this fixed approach leaves dose headroom in many patients: a single-institution series at the University of Wisconsin found that among 19 patients with post-cycle-one voxel-level SPECT/CT dosimetry, kidney and salivary gland absorbed doses tracked the VISION phase 3 benchmarks, and 15 of 19 patients could have safely received a seventh cycle and 18 of 19 an additional cycle based on a 24 Gy kidney and 20 Gy salivary gland threshold, while a smaller number needed early discontinuation or dose delay. In neuroendocrine tumour PRRT, the LUMEN and LUTADOSE studies found that tumour-absorbed dose measured after the first cycle predicts progression-free survival, reinforcing that a fixed four- or six-cycle schedule is a population average rather than a patient-specific optimum.

Several trials are now testing personalised dosing directly rather than relying on retrospective series. FLEX-MRT (NCT06216249, UCLA, randomised phase 2, about 90 patients) compares a flexible, SPECT/CT-response-guided schedule of up to 12 cycles with treatment holidays against the standard fixed six-cycle regimen, with 2-year survival as the primary endpoint. PRODIGY-2 (NCT06943495, CHU de Québec) is testing whether renal-dosimetry-guided activity escalation is feasible and safe compared with the fixed-activity regimen. In neuroendocrine tumours, DOBATOC (NCT04917484) is a randomised phase 2 testing kidney-dose-governed individualised dosing (targeting a 24 Gy cumulative kidney dose) against fixed dosing, with progression-free survival as the primary outcome.

This proposal is deliberately broader than the existing dosimetry-personalised-PRRT idea already in this graph, which is specific to neuroendocrine tumours: the claim here is that dosimetry-guided dosing should become the default approach across radioligand therapies generally, including PSMA-targeted treatment, not just PRRT.