Development of animal models for evaluation of technetium-99m renal tubular function agents

Diamide dimercaptide (N2S2) and triamide mercaptide (N3S) complexes of technetium-99m were shown to have potential use as a new class of renal tubular function agents. The biological evaluation of a number of these new Tc-99m chelating agents was performed in order to develop an optimal animal strategy for the screening of these agents as well as other potential complexes. Various animal models were studied to determine the potential correlation of the rate of renal clearance and the specificity for the renal transport system between the various animal species and humans. There was no single animal species which could routinely predict the performance of the complexes in humans. Therefore, the use of a select number of performance parameters, which were obtained from studies in the mouse, rat or dog were utilized to develop a set of criteria to predict the performance in humans. The use of these animal models minimized extrapolation errors, if limitation were placed on the amount of information which would be utilized from each of them. There were an number of complexes which appeared promising when evaluated in view of these species limitations. The evaluation of Tc-99m-mercaptoacetylglgcylglycylglycine (Tc-99m-MAG3) was found to perform will in all of the various animal models. Tc-99m-MAG3 was therefore utilized to develop an understanding for its pathway of elimination. The results from these studies show that Tc-99m-MAG3 is cleared from the body by the kidneys primarily by renal tubular secretion processes.