Synthesis, radiolabelling and biological evaluation of terminal oxamide derivatives of mercaptoacetyltriglycine

99mTc-MAG3 is widely used in clinical nuclear medicine as a potential replacement of 131I-OIH for renal function studies. The terminal carbonylglycine in the MAG3 backbone is assumed to be essential for maintaining its efficient renal handling characteristics. A number of MAG3-derivatives have been prepared and evaluated in which the terminal carbonylglycine sequence is substituted by an oxamide moiety in order to study the effect of the modified carbonylglycine sequence on the renal handling characteristics. These 'oxamide' derivatives have been synthesized starting from mercaptoacetic acid or cysteamine using the common synthetic procedures of peptide chemistry. These thiol-protected MAG3-precursors were labelled with 99mTC by an exchange method using tartrate as a complexing agent. Biodistribution studies in mice showed that some of these agents were cleared rapidly from the blood and efficiently excreted into the urine and displayed comparable renal excretion characteristics to those of 99mTc-MAG3. © 2002 John Wiley & Sons, Ltd.