99mTc(CO)3-nitrilotriacetic acid: a new renal radiopharmaceutical showing pharmacokinetic properties in rats comparable to those of 131I-OIH.

To develop a Tc-99m renal tracer with a capacity to measure effective renal plasma flow comparable to that of the clinical gold standard I-131-o-iodohippurate (I-131-OIH) and superior to that of (99m)Tco-mercaptoacetyltriglycine, which has a clearance only 50%-60% that of I-131-OIH, we investigated Tc-99m-tricarbonyl nitrilotriacetic acid (Na-2[Tc-99m(CO)(3)(NTA)]). This radiopharmaceutical, which is based on an aminopolycarboxylate ligand, is formed as a single species and has a dangling carboxylate group favoring tubular transport. Methods: Na-2[Tc-99m(CO)(3)(NTA)] was prepared by using commercially available NTA and an IsoLink kit and isolated by high-performance liquid chromatography. The stability of Na-2[Tc-99m(CO)(3)(NTA)] in isotonic saline was assessed for 24 hand was further evaluated by incubation in 0.1 M cysteine and histidine for 4 h at 37 degrees C. The biodistribution of Na-2[Tc-99m(CO)(3)(NTA)], coinjected with I-131-OIH as an internal control, was evaluated in 5 normal Sprague-Dawley rats at 10 min, 5 normal Sprague-Dawley rats at 60 min (group A), and 6 rats with renal pedicle ligation at 60 min (group B) after injection. Clearance and extraction fraction studies were conducted in 2 normal Sprague-Dawley rats, and urine and plasma from 2 additional normal rats each were analyzed for metabolites by high-performance liquid chromatography. Results: The radiochemical purity of Na-2[Tc-99m(CO)(3)(NTA)] was greater than 99%, the complex was stable for 24 h at physiologic pH, and the challenge experiments showed no degradation. In normal rats, the percentage dose in the urine at 10 and 60 min was 108% +/- 9% and 101% +/- 5%, respectively, that of I-131-OHI; minimal hepatic or gastrointestinal activity was demonstrated. In group B rats, Na-2[Tc-99m(CO)(3) (NTA)] was better retained in the blood and had less excretion into the bowel than did I-131-OIH (P < 0.01). The plasma clearances of Na-2[Tc-99m(CO)(3)(NTA)] and I-131-OIH were comparable but the extraction fraction of Na-2[Tc-99m(CO)(3)(NTA)] was 93.5% +/- 3.8%, compared with 67.9% +/- 6.1% for I-131-OIH. Plasma protein binding of Na-2[Tc-99m(CO)(3)(NTA)] averaged 67% +/- 7%, and red cell uptake was 7% +/- 2%. Conclusion: Na-2[Tc-99m(CO)(3)(NTA)] is stable, exists as a single species, and has pharmacodynamic properties in rats comparable to those of I-131-OIH.