Synthesis and radiolabelling studies of hynic conjugated PSMA targeting ligands

Development and clinical translation of small molecule PSMA-ligands labelled with a SPECT-radioisotope such as technetium-99m (^99mTc) 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 ^99mTc and the extent of ^99mTc radiolabelling was established using radioHPLC and radioTLC analysis. Two among the five ligands displayed radiochemical purity >90%, adequate for diagnostic applications.