Evaluation of Tc-99m-complexes with novel monoamine diamide (MADA) thiolate tetraligands: L-cysteine acetyldiglycine diethyl ester and L-beta-methylhomocysteinate acetyldiglycine ethyl ester

Compounds with a monoamine diamide (MADA) thiolate tetraligand structure (L -cysteine acetyldiglycine diethyl ester, L-CAG2D and L-beta -methylhomocyst einate acetyldiglycine ethyl ester, L-HAG2ME) were synthesized and labelled with Tc-99m to investigate the Tc-99m-complexation characteristics of thes e tetraligands. On reversed-phase HPLC, Tc-99m-L-CAG2D and Tc-99m-L-HAG2ME each give two peaks, probably isomers. During electrophoresis, all isomers migrate towards the anode indicating a net anionic charge, Octanol-buffer p artition coefficients were respectively -0.47 and -0.05 For the isomers of Tc-99m-L-CAG2D and -0.51 and -0.32 for the isomers of Tc-99m-L-HAG2ME. In a ddition, brain uptake of all HPLC- isolated isomers was low and did not exc eed 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 compl exation with Tc-99m resulting in hydrophilic, negatively charged Tc-99m-com plexes which do not exhibit significant brain uptake in mice.