Synthesis and biological evaluation of technetium-99m MAG3 as a hippuran replacement.
A new technetium-chelating agent based on a triamide monomercaptide tetradentate set of donor groups, mercaptoacetylglycylglycylglycine (MAG3), was synthesized and evaluated. Chelation with 99mTc resulted in a single radiochemical product as expected. Studies in mice of [99mTc]MAG3 indicated excretion rates faster than omicron-iodohippurate (OIH) both in normal and in probenecid treated animals. Specificity for renal excretion was essentially complete. Clearance studies in rats resulted in 2.84 ml/min/100 g for [99mTc]MAG3, 2.17 for OIH, and 1.29 for [125I]iothalamate. Extraction efficiencies were 85% for [99mTc]MAG3, 69% for OIH and 39% for [125I]iothalamate. Probenicid depressed the clearance both of [99mTc]MAG3 and OIH at 25 and 50 mg/kg/hr, but to a greater extent with [99mTc]MAG3. The greater effect is offset, however, by the larger fraction secreted by the renal tubular cells. The animal results suggest that [99mTc]MAG3 may be a useful alternative to [131I]OIH.
D000818:Animals; D005260:Female; D007465:Iodohippuric Acid; D007668:Kidney / Q000000981:diagnostic imaging*; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000138:chemical synthesis*; D011339:Probenecid / Q000494:pharmacology; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D013667:Technetium / Q000138:chemical synthesis*; D017263:Technetium Tc 99m Mertiatide; D014018:Tissue Distribution
D009842:Oligopeptides; D007465:Iodohippuric Acid; D017263:Technetium Tc 99m Mertiatide; D013667:Technetium; D011339:Probenecid