AIM: To analyze the safety, efficacy and dosimetry of Lu-177 labeled prostate specific membrane antigen (PSMA) ligand 617 in patients with progressive metastatic castration-resistant prostate cancer (mCRPC), in comparison with Lu-177 PSMA I&T.
METHODS:  Lu-177 PSMA-617 radioligand therapy (PRLT) was performed in 64 mCRPC patients. The median administered activity per treatment was 6 GBq. Ga-68 PSMA PET/CT was used for patient selection and follow-up. Hematological status, renal and hepatic function and serum prostate specific antigen (PSA) levels were documented before and after therapy.
RESULTS: Lu-177 PSMA-617 demonstrated intense accumulation in the metastases. The absorbed tumor dose was 6.3 mGy/MBq (median). Parotid glands received a higher dose (1.0 mGy/MBq) than kidneys (0.65 mGy/MBq). All patients tolerated the therapy well without any acute adverse effects. Mild xerostomia was observed in 5 patients. G1 hematological toxicity was noticed in 13 patients, G2 in 5 and G3-4 pancytopenia in 2 patients. Mild erythrocytopenia was the commonest sequel. Higher-grade toxicity was observed in patients (n=7) having received chemotherapy or Ra-223 treatment before. The severity of pain was significantly reduced in 6/17 (35.3 %) symptomatic patients after PRLT. Decrease in PSA was noted in 48/64 (76.9 %) patients. Molecular response evaluation (Ga-68 PSMA PET/CT) in 29 patients followed up after at least 2 cycles revealed complete remission (CR) in 3, partial remission (PR) in 12, stable disease (SD) in 5 and progressive disease (PD) in 9 patients. CT exhibited PR in 8, SD in 14, and PD in 7 patients. The median overall survival is yet to be reached and progression-free survival was 12.3 months.
CONCLUSION: Lu-177 PSMA-617 appears to be safe and effective in progressive mCRPC. The kinetics and dosimetry are similar to Lu-177 PSMA-I&T, the first-ever PSMA inhibitor used at our center.