Tc-99m labeled PSMA-617 as a potential SPECT radiotracer for prostate cancer diagnostics: Complexation optimization and its in vitro/vivo evaluation

Technetium-99m (Tc-99m) is the most employed radionuclide in nuclear imaging diagnostics worldwide for many diseases. The ideal physiochemical properties of Tc-99m (such as half-life and pure gamma energy) make it favorable for Single Photon Emission Computed Tomography (SPECT). In this study, we aim to expand the utilization of Tc-99m radiopharmaceutical toward prostate cancer diagnostics which is currently no FDA approved products and has been intensively examined for a potential candidate. The new formulation for Tc-99m complexation with PSMA-617, a current ligand for radionuclide therapy of prostate cancer with lutetium-177 (Lu-177), has been investigated. Co-complexation with citrate was utilized to improve the labeling efficiency by over 97 %. The stability of the new radiopharmaceutical was in vitro evaluated confirming that the Tc-99m labeled PSMA-617 remained stable for over a single half-life of Tc-99m in normal saline solution and in human serum. The in vivo study in the LNCaP xenografted mouse model confirmed a high selectivity of the new tracer toward prostate cancer.