225Ac-PSMA-617 for PSMA-Targeted α-Radiation Therapy of Metastatic Castration-Resistant Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently, we started the first-in-human treatment with an α-radionuclide-labeled PSMA ligand. Although the case series is still ongoing, we here report in advance about two patients in highly challenging clinical situations who showed a complete response to 225Ac-PSMA-617 therapy.

68Ga-PSMA-11 PET/CT validated the presence of the PSMA-positive tumor phenotype. A 100-kBq activity of 225Ac-PSMA-617 per kilogram of body weight was administered bimonthly. Prostate-specific antigen response and hematologic toxicity were measured at least every 4 wk. Restaging was performed with 68Ga-PSMA-11 PET/CT.

Both patients experienced a prostate-specific antigen decline to below the measurable level and showed a complete response on imaging. No relevant hematologic toxicity was observed. Xerostomia was the only mentionable clinical side effect.

Targeted α-therapy with 225Ac-PSMA-617, although still experimental, obviously has strong potential to significantly benefit advanced-stage prostate cancer patients.

Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2016 Jul 07 [Epub]

Clemens Kratochwil, Frank Bruchertseifer, Frederik L Giesel, Mirjam Weis, Frederik A Verburg, Felix Mottaghy, Klaus Kopka, Christos Apostolidis, Uwe Haberkorn, Alfred Morgenstern

Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany ., European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe, Germany., Department of Nuclear Medicine, University Hospital Heidelberg, Heidelberg, Germany., Department of Nuclear Medicine, RWTH University Hospital Aachen, Aachen, Germany; and., Division of Radiopharmaceutical Chemistry, German Cancer Research Center, Heidelberg, Germany.