Synthesis of tritium-labeled Lu-PSMA-617: Alternative tool for biological evaluation of radiometal-based pharmaceuticals

Abstract

This project focuses on the generation and evaluation of functional alternatives to radiometal-based pharmaceuticals supporting basic research and the in vitro developmental phase. Employing robust tritium chemistry and non-radioactive metal surrogates in two synthetic and labeling strategies resulted in ([ring-³H]Nal)PSMA-617 and ([α,ß-³H]Nal)PSMA-617. In particular, ([α,ß-³H]Nal)Lu-PSMA-617 exhibited high radiolytic as well as metal-complex stability and was compared to the clinically-established radiopharmaceutical [¹⁷⁷Lu]Lu-PSMA-617. The cell-based assays confirmed the applicability of ([α,ß-³H]Nal)Lu-PSMA-617 as a substitute of [¹⁷⁷Lu]Lu-PSMA-617 in pre-clinical biological settings.

Keywords: Labeling chemistry; PSMA ligands; PSMA-617; Pharmaceutical development; Prostate cancer; Radiometals; Tritium.