Organic synthesis and biological evaluation of novel "3+1" mixed ligands of technetium-99m Gabapentin as receptor imaging agents

This work focuses on the "3 + 1" mixed ligands of Tc-99m labeled Gabapentin as alpha 2 delta receptor imaging agents in the brain. Gabapentin 1-(aminomethyl) cyclohexanacetic acid as monodentate and two tridentates: tridentate A; 3-(2-imino- thiozolidin-4-one)-quinozoline-4-(3H)-one and tridentate B; N-(4-chlorophenyl)-2-imino-2H-chromene-3-Carbothioamide which were synthesized and characterized by infrared analysis (IR), H-1 nuclear magnetic resonance (NMR), and mass spectrum. Tc-99m-complexes were prepared by the "3 + 1" mixed ligand approach. The labeling conditions were optimized and the complexes was extracted by chloroform and purified by high performance liquid chromatography. Tc-99m-complexs were lipophilic and stable for at least 8-12 h at room temperature. The biodistribution of the Tc-99m-complexes was evaluated in mice. The brain uptake was 4.5% and 3.5% ID/g (percentage of the injected dose per gram) at 5 min, and the retention was 1.5% and 1.7% ID/g at 120 min for Tc-99m-complex A and Tc-99m-complex B, respectively.