Assessing PSMA Receptor Availability Using 68Ga-PSMA-11 PET/CT Following 177Lu-PSMA-617 Therapy Administration

Prostate cancer treatment with 177Lu-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 177Lu-PSMA-617 based on the uptake of 68Ga-PSMA-11 on subsequent PET.

We performed 68Ga-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. SUVmean of tumors (N=27) and organs, stratified by early (<2 h) and late (~3 d) post-therapy PET imaging, were compared with baseline PET.

There were large decreases in SUVmean 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).

There are measurable decreases in PSMA binding following 177Lu-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.