Total chemical synthesis of PSMA-617: an API for prostate cancer endotherapeutic applications

Abstract Synthesis of PSMA-617, a peptide based ligand used in the preparation of nuclear medicine, 177 Lu-PSMA-617, for the treatment of prostate cancer, is demonstrated in 6 steps, starting from appropriately protected amino acid building blocks. A solution phase Boc-strategy was adopted for the synthesis of peptide, wherein deprotection of carbamate group using HCl (g), was employed as the key step. The synthesis furnished PSMA-617 in purity >99.5 % as confirmed by HPLC analysis. ESI-MS and NMR analysis supported the structural integrity of the compound. The synthesized ligand was radiolabelled using 177 Lu to generate the desired radiopharmaceutical, 177 Lu-PSMA-617, in radiochemical purity >98 %, as revealed by radio HPLC and TLC analysis. This establishes its potential as a nuclear medicine for therapeutic application.