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

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 (177)Lu-PSMA617 therapy on the basis of PSMA-targeted (68)Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging ((68)Ga-PSMA-HBED-CC and (18)F-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 (177)Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed.

(177)Lu-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 (177)Lu-PSMA617 and (68)Ga-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 (177)Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study.

European journal of nuclear medicine and molecular imaging. 2017 Jan 12 [Epub ahead of print]

Lorenza Scarpa, Sabine Buxbaum, Dorota Kendler, Katharina Fink, Jasmin Bektic, Leonhard Gruber, Clemens Decristoforo, Christian Uprimny, Peter Lukas, Wolfgang Horninger, Irene Virgolini

Department of Nuclear Medicine, Medical University Innsbruck, Anichstraße 35, A-6020, Innsbruck, Austria., Department of Urology, Medical University of Innsbruck, Innsbruck, Austria., Department of Radiology, Medical University of Innsbruck, Innsbruck, Austria., Department of Radiotherapy / Radiation Oncology, Medical University of Innsbruck, Innsbruck, Austria., Department of Nuclear Medicine, Medical University Innsbruck, Anichstraße 35, A-6020, Innsbruck, Austria. .