Radiosynthesis and characterization of GSH 68GA99mTC complex and its bioevaluation in experimental carcinogenesis

Abstract

The present study was designed to evaluate the role of 68Ga-GSH and 99mTc-GSH in experimentally induced colon cancer. The radiolabeling was performed by the direct radiolabeling method with radiolabeling efficiency of gt 72 % for 68Ga-GSH radio-complex and gt 95 % for 99mTc-GSH radio-complex. From the molecular simulation studies it was observed that cold glutathione most stable conformer (Ligand Pose 9) bind to the active site of residues of enzyme transpeptidase with greater affinity represented by a low docking score -46.08. In silico docking studies were performed that revealed that 68Ga-GSH (ligand pose 7) complex with 4GG2 with high affinity and affording D-Score -61.08. The favourable D-Score can be attributed to its strong hydrogen, ionic and hydrophobic interaction with amino acids of the active site of the receptor. Molecular docking results also showed that99mTc-GSH gets well accommodated in the binding pocket of gamma-glutamyltranspeptidase in comparable orientation with lowest estimated binding energy -81.90. Cell culture toxicity assays i.e. 3-(4,5-dimethylthiazolyl-2)-2,5- diphenyltetrazolium bromide (MTT) and trypan blue exclusion assay showed that both the radiocomplex s are non-toxic to HT 29 cells and as such indicates their potential for in vivo applications. The biodistribution results of these radiocomplxe s indicated the colon tumour delineating features. newline