Prostate-specific membrane antigen (PSMA), highly expressed in prostate cancer, is a promising target for radionuclide therapy. Auger electron-emitting radionuclides are well suited for targeted radionuclide therapy if they can be delivered close to the DNA of the targeted cells. This preclinical study evaluated the theranostic pair [55/58mCo]Co-DOTA-PSMA-617 for PET imaging and Auger electron therapy of prostate cancer. [58mCo]Co-DOTA-PSMA-617 was successfully prepared with > 99% radiochemical yield and purity. In vitro, uptake and subcellular distribution assays in PSMA-positive prostate cancer cells showed PSMA-specific uptake with high cell-associated activity in the nucleus. Incubation with [58mCo]Co-DOTA-PSMA-617 reduced cell viability and clonogenic survival in a significant dose-dependent manner (p < 0.05). Biodistribution of xenografted mice showed high specific tumor uptake of the cobalt-labeled PSMA ligand for all time points with rapid clearance from normal tissues, which PET imaging confirmed. In vivo, therapy with [58mCo]Co-DOTA-PSMA-617 in tumor-bearing mice demonstrated significantly increased median survival for treated mice compared to control animals (p = 0.0014). In conclusion, [55/58mCo]Co-DOTA-PSMA-617 displayed excellent in vitro and in vivo properties, offering significant survival benefits in mice with no observed toxicities.
Scientific reports. 2023 Nov 01*** epublish ***
Christina Baun, Johan Hygum Dam, Malene Grubbe Hildebrandt, Jesper Dupont Ewald, Bjarne Winther Kristensen, Vigga Sand Gammelsrød, Birgitte Brinkmann Olsen, Helge Thisgaard
Department of Nuclear Medicine, Odense University Hospital, Kløvervænget 47, 5000, Odense C, Denmark., Department of Clinical Research, University of Southern Denmark, Odense, Denmark., Department of Nuclear Medicine, Odense University Hospital, Kløvervænget 47, 5000, Odense C, Denmark. .