PT - JOURNAL ARTICLE AU - Lipowska, Malgorzata AU - Marzilli, Luigi G. AU - Taylor, Andrew T. TI - <sup>99m</sup>Tc(CO)<sub>3</sub>-Nitrilotriacetic Acid: A New Renal Radiopharmaceutical Showing Pharmacokinetic Properties in Rats Comparable to Those of <sup>131</sup>I-OIH AID - 10.2967/jnumed.108.058768 DP - 2009 Mar 01 TA - Journal of Nuclear Medicine PG - 454--460 VI - 50 IP - 3 4099 - http://jnm.snmjournals.org/content/50/3/454.short 4100 - http://jnm.snmjournals.org/content/50/3/454.full SO - J Nucl Med2009 Mar 01; 50 AB - 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%−60% that of 131I-OIH, we investigated 99mTc-tricarbonyl nitrilotriacetic acid (Na2[99mTc(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[99mTc(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[99mTc(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[99mTc(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[99mTc(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 131I-OIH; minimal hepatic or gastrointestinal activity was demonstrated. In group B rats, Na2[99mTc(CO)3(NTA)] was better retained in the blood and had less excretion into the bowel than did 131I-OIH (P &lt; 0.01). The plasma clearances of Na2[99mTc(CO)3(NTA)] and 131I-OIH were comparable, but the extraction fraction of Na2[99mTc(CO)3(NTA)] was 93.5% ± 3.8%, compared with 67.9% ± 6.1% for 131I-OIH. Plasma protein binding of Na2[99mTc(CO)3(NTA)] averaged 67% ± 7%, and red cell uptake was 7% ± 2%. Conclusion: Na2[99mTc(CO)3(NTA)] is stable, exists as a single species, and has pharmacodynamic properties in rats comparable to those of 131I-OIH.