Synthesis and radiolabelling studies of hynic conjugated PSMA targeting ligands

Abstract Development and clinical translation of small molecule PSMA-ligands labelled with a SPECT-radioisotope such as technetium-99m ( 99m Tc) has immense importance, particularly in countries with high population density and limited amenities. Towards this, herein we report the total chemical synthesis of five Hynic (2-hydrazinonicotinic acid) conjugated PSMA ligands employing the solution phase alloc chemistry. A linear synthetic strategy was adopted for the construction of all target molecules. The amino acids that act as spacers were synthesized from corresponding unprotected precursors in 60–65 % overall yield. All the synthesized ligands were appropriately characterized using NMR, HPLC, and MS, to confirm their structural veracity. After the successful synthesis, all the ligands were radiolabelled using 99m Tc and the extent of 99m Tc radiolabelling was established using radioHPLC and radioTLC analysis. Two among the five ligands displayed radiochemical purity >90 %, adequate for diagnostic applications.