Syntheses and radiolabeling of cysteine-oximes and pharmacological behaviour of their 99mTc complexes

Abstract

Synthesis of two novel ligands using 2-oximino-butan-3-one and l-ethyl cysteinate is described. The synthetic procedure involved the formation of Schiff's base by the condensation of the amino group of l-ethyl cysteinate with the carbonyl group of 2-oximino-butan-3-one to provide the ligand I, N′(butan-2-enyl-3-oximino)ethyl cysteinate, followed by reduction of the Schiff's base with sodium borohydride to ligand II, N′(3-oximinobutyl)ethyl cysteinate. The ligands were characterised by NMR spectroscopy. Complexation studies with 99mTc were carried out using stannous tartrate as the reducing agent. The complexes were characterised by paper chromatography, thin layer chromatography and paper electrophoresis techniques. The complexes are formed in high yields when the reactions were carried out at pH 7–9. The 99mTc complex with ligand I is formed instantaneously while the 99mTc complex with ligand II is formed at a slower rate. The complexes were found to be neutral but the lipophilicity of the complex with ligand I was higher than that of the complex of ligand II. The stability of the complex with ligand I was relatively poor as compared to that of the complex with ligand II. Biodistribution studies of the 99mTc complexes of ligand I and II showed rapid blood clearance with hepatobiliary uptake. Renal excretion of the complex of ligand II was more than that observed for the complex of ligand I. The complexes did not show significant uptake in brain in spite of their favourable properties such as neutrality, lipophilicity and structural similarity with both ECD and HMPAO.