Purpose: Prostate cancer treatment with 177 Lu-PSMA-617 depends on specific binding to the PSMA protein. If receptors become saturated by the radioligand, the uptake of the drug may be affected. Our goal was to measure the pharmacological effect of standard 7.4 GBq (200 mCi) administration of 177 Lu-PSMA-617 based on the uptake of 68 Ga-PSMA-11 on subsequent PET. Patients and Methods: We performed 68 Ga-PSMA-11 PET/CT within 0.5–75 hours after cycle 1 of therapy administration in 6 patients with metastatic castrate-resistant prostate cancer who volunteered for imaging. SUV mean of tumors (N=27) and organs, stratified by early (<2 h) and late (~3 d) post-therapy PET imaging, were compared with baseline PET. Results: There were large decreases in SUV mean for tumor, kidney, parotid gland, and liver among patients imaged early after therapy, with an average change in tumor SUV of −45% (95% CI: −66% to −25%; P <0.001). In contrast, only mild persistent declines in SUV were observed in those scanned late, with an average change in tumor SUV of −9% (95% CI: −33% to 16%; P =0.42). Conclusions: There are measurable decreases in PSMA binding following 177 Lu-PSMA-617 that resolve over time. As trials consider alternative therapeutic strategies, increasing dosage per cycle alone may not proportionally increase tumor uptake. Our findings warrant validation with a larger number of subjects, standardized post-therapy scan timing, and advanced pharmacokinetic analyses.
Roseland et al. (2026) studied this question.