Radiochemical studies of Tc-99m complexes of modified cysteine ligands andbifunctional chelating agents

The synthesis of four novel ligands using the amino-acid cysteine and its e thyl carboxylate derivative is described. The synthetic method involves a t wo-step procedure, wherein the intermediate Schiff base formed by the conde nsation of the amino group of the cysteine substrate and salicylaldehyde is reduced to give the target ligands. The intermediates and the final produc ts were characterized by high resolution nuclear magnetic resonance spectro scopy. Complexation studies of the ligands with Tc-99m were optimized using stannous tartrate as the reducing agent under varying reaction conditions. The complexes were characterized using standard quality control techniques such as thin layer chromatography, paper electrophoresis, and paper chroma tography. Lipophilicities of the complexes were estimated by solvent extrac tion into chloroform. Substantial changes in net charge and lipophilicity o f the Tc-99m complexes were observed on substituting the carboxylic acid fu nctionality in ligands I and II with the ethyl carboxylate groups (ligands III and IV). All the ligands formed Tc-99m complexes in high yield. Whereas the complexes with ligands I and II were observed to be hydrophilic in nat ure and not extractable into CHCl3, ligands III and IV resulted in neutral and lipophilic Tc-99m complexes. The Tc-99m complex with ligand III was not stable and on storage formed a hydrophilic and nonextractable species. The biodistribution of the complexes of ligands I and II showed that they clea red predominantly through the kidneys, whereas the complexes with ligands I II and IV were excreted primarily through the hepatobiliary system. No sign ificant brain uptake was observed with the Tc-99m complexes with ligands II I and IV despite their favorable properties of neutrality, lipophilicity, a nd conversion into a hydrophilic species. These ligands offer potential for use as bifunctional chelating agents. (C) 1999 Elsevier Science Inc. All r ights reserved.