PSMA-targeted radionuclide therapy of metastatic castration-resistant prostate cancer with Lu-177 labeled PSMA-617.

Prostate-specific membrane antigen (PSMA) is an excellent target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). Besides high affinity and long tumor retention, the DOTA-conjugated ligand PSMA-617 has low kidney uptake making it an excellent choice for therapeutic application. We retrospectively report our experience with (177)Lu-PSMA-617 targeted radionuclide therapy in a case series of mCRPC patients resistant to other treatments.

Patients with PSMA-positive tumor phenotypes were selected by molecular imaging. 30 patients received 1-3 cycles of (177)Lu-PSMA-617. During therapy pharmacokinetics and radiation-dosimetry were evaluated. Blood cell count was checked every two weeks after the first and every four weeks after succeeding cycles. PSA was determined every four weeks. Radiological restaging was performed after three cycles.

21/30 patients had a PSA response; in 13/30 the PSA decreased >50%. After 3 cycles 8/11 patients achieved a sustained PSA response (>50%) for over 24 weeks which also correlated with radiological response (decreased lesion number and size). Normally, acute hematotoxicity was mild. Diffuse bone marrow involvement was a risk factor for higher grade myelosuppression but could be identified by PSMA-imaging in advance. Xerostomia, nausea and fatigue occurred sporadically (<10%). Clearance of non-tumor-bound tracer is predominantly renal and widely completed by 48h. Safety dosimetry reveals kidney doses of approx. 0.75 Gy/GBq, red-marrow 0.03 Gy/GBq, salivary glands 1.4 Gy/GBq; irrespective of tumor burden and consistent on subsequent cycles. Mean tumor absorbed dose ranged 6-22 Gy/GBq during cycle-1.

(177)Lu-PSMA-617 is a promising new option for therapy of mCRPC and deserves more attention in larger prospective trials.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2016 Mar 16 [Epub ahead of print]

Clemens Kratochwil, Frederik L Giesel, Melsa Stefanova, Martina Benešová, Marcus Bronzel, Ali Afshar-Oromieh, Walter Mier, Matthias Eder, Klaus Kopka, Uwe Haberkorn

University Hospital Heidelberg, Germany;, University Hospital Heidelberg, Germany;, University Hospital Heidelberg, Germany;, German Cancer Research Center (dkfz);, ABX-CRO., University Hospital Heidelberg, Germany;, University Hospital Heidelberg, Germany;, German Cancer Research Center (dkfz);, German Cancer Research Center (dkfz);, University Hospital Heidelberg, Germany;