Tc(CO)3-Nitrilotriacetic Acid: A New Renal Radiopharmaceutical Showing Pharmacokinetic Properties in Rats Comparable to Those of 131I-OIH

To develop a 99mTc renal tracer with a capacity to measure effective renal plasma flow comparable to that of the clinical gold standard 131I-o-iodohippurate (131I-OIH) and superior to that of 99mTcO-mercaptoacetyltriglycine, which has a clearance only 50%260% that of 131I-OIH, we investigated 99mTc-tricarbonyl nitrilotriacetic acid (Na2[Tc(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: Na2[Tc(CO)3(NTA)] was prepared by using commercially available NTA and an IsoLink kit and isolated by high-performance liquid chromatography. The stability of Na2[Tc(CO)3(NTA)] in isotonic saline was assessed for 24 h and was further evaluated by incubation in 0.1 M cysteine and histidine for 4 h at 37 C. The biodistribution of Na2[Tc (CO)3(NTA)], coinjected with 131I-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 Na2[Tc(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% 6 9% and 101% 6 5%, respectively, that of 131I-OIH; minimal hepatic or gastrointestinal activity was demonstrated. In group B rats, Na2[Tc(CO)3 (NTA)] was better retained in the blood and had less excretion into the bowel than did 131I-OIH (P , 0.01). The plasma clearances of Na2[Tc(CO)3(NTA)] and 131I-OIH were comparable, but the extraction fraction of Na2[Tc(CO)3(NTA)] was 93.5% 6 3.8%, compared with 67.9% 6 6.1% for 131I-OIH. Plasma protein binding of Na2[Tc(CO)3(NTA)] averaged 67% 6 7%, and red cell uptake was 7% 6 2%. Conclusion: Na2[Tc (CO)3(NTA)] is stable, exists as a single species, and has pharmacodynamic properties in rats comparable to those of 131I-OIH.