Preclinical evaluation of 99mTc(CO) 3-aspartic-N- monoacetic acid, a renal radiotracer with pharmacokinetic properties comparable to 131I-o-iodohippurate

Abstract

In an ongoing effort to develop a renal tracer with pharmacokinetic properties comparable to p-aminohippurate and superior to those of both 99mTc-mercaptoacetyltriglycine and 131I-o-iodohippurate ( 131I-OIH), we evaluated a new renal tricarbonyl radiotracer based on the aspartic-N-monoacetic acid (ASMA) ligand, 99mTc(CO) 3(ASMA). The ASMA ligand features 2 carboxyl groups and an amine function for the coordination of the { 99mTc (CO) 3} + core as well as a dangling carboxylate to facilitate rapid renal clearance. Methods: rac-ASMA and L-ASMA were labeled with a 99mTc- tricarbonyl precursor, and radiochemical purity of the labeled products was determined by high-performance liquid chromatography. Using 131I-OIH as an internal control, we evaluated biodistribution in normal rats with 99mTc(CO) 3(ASMA) isomers and in rats with renal pedicle ligation with 99mTc (CO) 3(rac-ASMA). Clearance studies were conducted in 4 additional rats. In vitro radiotracer stability was determined in phosphate-buffered saline, pH 7.4, and in challenge studies with cysteine and histidine. 99mTc(CO) 3(ASMA) metabolites in urine were analyzed by high-performance liquid chromatography. Results: Both 99mTc(CO) 3(ASMA) preparations had greater than 99% radiochemical purity and were stable in phosphate-buffered saline, pH 7.4, for 24 h. Challenge studies on both revealed no significant displacement of the ligand. In normal rats, the percentage injected dose in urine at 10 and 60 min for both preparations averaged, respectively, 103% and 106% that of 131I-OIH. The renal clearances of 99mTc(CO) 3(rac-ASMA) and 131I-OIH were comparable (P = 0.48). The tracer was excreted unchanged in the urine, proving its in vivo stability. In pedicle-ligated rats, 99mTc(CO) 3(rac-ASMA) had less excretion into the bowel (P < 0.05) than did 131I-OIH and was better retained in the blood (P < 0.05). Conclusion: Both 99mTc (CO) 3(ASMA) complexes have pharmacokinetic properties in rats comparable to or superior to those of 131I-OIH, and human studies are warranted for their further evaluation. Copyright © 2012 by the Society of Nuclear Medicine and Molecular Imaging, Inc.