‘4+1’ Mixed Ligand Strategy for the Preparation of 99m Tc-Radiopharmaceuticals for Hypoxia Detecting Applications (original) (raw)

The '4 + 1' mixed ligand strategy enables radiolabeling of biomolecules with 99m Tc at low ligand concentration without affecting it's in vivo biological activity. The '4 + 1' mixed-ligand complexes consist of central Tc(III) metal atom coordinated to a tetradentate tripodal chelator 2,2',2''-nitrilotriethanethiol (NS 3) and a monodentate isocyanide group tethered to a biomolecule. The present work describes the use of '4 + 1' mixed ligand strategy to design radiopharmaceuticals for the detection of tissue hypoxia in vivo. Isocyanide derivatives of two nitroimidazoles, viz. 2-nitroimidazole (2NimNC) and metronidazole (MetNC), were synthesized and radiolabeled with 99m Tc using '4 + 1' mixed ligand approach. The complexes [ 99m Tc(NS 3)(2NimNC)] and [ 99m Tc(NS 3)(MetNC)] could be prepared in excellent yield (> 90%). The structure of 99m Tc-complexes prepared at the no-carrier-added (nca) level was corroborated by spectroscopic analysis of corresponding rhenium analogues at the macroscopic level. Preliminary biological evaluation of the two nitroimidazole-'4 + 1' mixed ligand complexes in Swiss mice bearing fibrosarcoma tumor showed uptake and retention of the complexes in tumor.