Design,Organic Synthesis and Biological Evaluation of Novel "3 +1" Mixed Ligands of Technetium-99m Complexes as Receptors Imaging Agents

Abstract

The "3+1" mixed ligand approach is useful in the development of new 99mTc radioligands for the imaging of brain receptors. Further effort is needed to obtain a much more lypophilic and stable complex, and a specific binding capacity to brain receptors is required to enhance brain uptake. A tridentate ligand N-(4-Chlorophenyl)- 2-imino-2H-Chromene-3-Carbothioamide has been synthesized and characterized by IR, 1H-NMR and mass spectroscopy. The 99mTc complex B was prepared by a ligand exchange reaction with 99mTc glucoheptonate as a potential receptor imaging agent. Ligands ratio, reaction time, pH of reaction mixture and temperature were optimized to achieve high substitution yield and radiochemical purity. The labelling efficiency and stability of the produced complex B were determined by thin layer chromatography, the organic solvent extraction method and high performance liquid chromagraphy (HPLC). The biodistribution of the labeled compound was performed by using mice. The ligand studied provides efficient labeling (75%) at 70ºC for 30 min. at pH 7. The complex B is good lipophilic complex (logP=1.4) and stable for at least 8–12 hours at room temperature (25ºC) in vitro. The 99mTc complex B was purified by HPLC and sterilize by Millipore filter then injected in mice. The biodistribution studies for 99mTc complex showed selective brain uptake which is 1.4% at 5 min post injection with good retention in mice brain for time sufficient to perform brain imaging.