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^99mTc(CO)₃-Nitrilotriacetic Acid: A New Renal Radiopharmaceutical Showing Pharmacokinetic Properties in Rats Comparable to Those of ¹³¹I-OIH

¹ Department of Radiology, Emory University, Atlanta, Georgia; and ² Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana

Correspondence: For correspondence or reprints contact: Andrew T. Taylor, Department of Radiology, Emory University, Atlanta, GA 30322. E-mail: ataylor{at}emory.edu

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 < 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.

Key Words: ^99mTc-tricarbonyl • renal radiopharmaceuticals • ^99mTc(CO)₃(NTA) • ¹³¹I-ortho-iodohippurate (¹³¹I-OIH) • ^99mTc-mercaptoacetyltriglycine (^99mTcO-MAG3)

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.

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