The ⁶⁸Ga/¹⁷⁷Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUV_max values and absorbed dose estimates.

Abstract

A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Ten consecutive mCRPC patients were selected for ¹⁷⁷Lu-PSMA617 therapy on the basis of PSMA-targeted ⁶⁸Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging (⁶⁸Ga-PSMA-HBED-CC and ¹⁸F-NaF PET/CT) was performed after 2 and 3 therapy cycles (each 6.1 ± 0.3 GBq, range 5.4-6.5 GBq) given intravenously over 30 minutes, 9 ± 1 weeks apart. PET/CT scans were compared to ¹⁷⁷Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed. ¹⁷⁷Lu-PSMA617 dosimetry indicated high tumour doses for skeletal (3.4 ± 1.9 Gy/GBq; range 1.1-7.2 Gy/GBq), lymph node (2.6 ± 0.4 Gy/GBq; range 2.3-2.9 Gy/GBq) as well as liver (2.4 ± 0.8 Gy/GBq; range 1.7-3.3 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 18 ± 0.3 GBq. Three patients showed partial remission, three mixed response, one stable and three progressive disease. Decreased ¹⁷⁷Lu-PSMA617 and ⁶⁸Ga-PSMA-HBED-CC uptake (mean SUVmax values 20.2 before and 15.0 after 2 cycles and 11.5 after 3 cycles, p < 0.05) was found in 41/54 skeletal lesions, 12/13 lymph node metastases, 3/5 visceral metastases and 4/4 primary PC lesions. Due to substantial individual variance, dosimetry is mandatory for a patient-specific approach following ¹⁷⁷Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study.