Evaluation of 99mTc-mercaptoacetyltripeptides in mice and a baboon

Different derivatives of MAG, carrying amino acids such as D- or L-alanine, D-serine, D-2-aminobutyric acid, D-valine or D-phenylglycine were synthesized and their 99mTc-complexes were evaluated in mice and a baboon. The efficiency of renal handling of the examined 99mTc-complexes is influenced not only by their lipophilicity but also to a great extent by their configuration and the site of substitution. The renal excretion characteristics of 99mTc-MAGAG-DA are superior to those of 99mTc-MAG3 and the studied 99mTc-complexes in both animal species. In an attempt to improve the renal handling of 99mTc-MAG3 and to evaluate the effect of derivatization we have synthesized different derivatives of MAG3 in which one or more glycyl groups are replaced by other amino acids such as D- or L-alanine, D-serine, D-2-aminobutyric acid, D-valine or D-phenylglycine. Due to the presence of a chiral centre in the ligand core, exchange labelling of each of the MAG3 derivatives results in the formation of two diastereomeric technetium complexes. These isomers were separated by HPLC and evaluated in mice. Biodistribution in mice indicates that the efficiency of renal handling of the examined 99mTc-complexes is not only influenced by their lipophilicity but also to a great extent by their configuration. The renal excretion characteristics of isomer DA of 99mTc-MAGAG in mice are superior to those of all other studied 99mTc-complexes and also of the reference compound [131I]Hippuran. The isomers LB of several alanyl derivatives of 99mTc-MAG3 exhibit a pronounced renal retention in both mice and baboon. The results of the evaluation in a baboon confirm the superiority of 99mTc-MAGAG-DA over 99mTc-MAG3 and the other studied 99mTc-complexes.