Evaluation of99mTc-complexes with novel monoamine diamide (MADA) thiolate tetraligands:L-cysteine acetyldiglycine diethyl ester andL-β-methylhomocysteinate acetyldiglycine ethyl ester

Abstract

Compounds with a monoamine diamide (MADA) thiolate tetraligand structure (L-cysteine acetyldiglycine diethyl ester, L-CAG2D and L-β-methylhomocysteinate acetyldiglycine ethyl ester, L-HAG2ME) were synthesized and labelled with 99mTc to investigate the 99mTc-complexation characteristics of these tetraligands. On reversed-phase HPLC, 99mTc-L-CAG2D and 99mTc-L-HAG2ME each give two peaks, probably isomers. During electrophoresis, all isomers migrate towards the anode indicating a net anionic charge. Octanol-buffer partition coefficients were respectively −0.47 and −0.05 for the isomers of 99mTc-L-CAG2D and −0.51 and −0.32 for the isomers of 99mTc-L-HAG2ME. In addition, brain uptake of all HPLC-isolated isomers was low and did not exceed 0.1% of injected dose at 2 min, 10 min or 30 min post injection. It may be concluded that the MADA-type ligands lose their amine proton upon complexation with 99mTc resulting in hydrophilic, negatively charged 99mTc-complexes which do not exhibit significant brain uptake in mice. Copyright © 2000 John Wiley & Sons, Ltd.