Preclinical Evaluation of 99mTc(CO)3-Aspartic-N-Monoacetic Acid, a Renal Radiotracer with Pharmacokinetic Properties Comparable to 131I-o-Iodohippurate

• Authors: Malgorzata Lipowska, Emory University; Jeff Klenc, Emory University; Luigi G. Marzilli, Louisiana State University; Andrew T Taylor Jr., Emory University
• Journal Title: Journal of Nuclear Medicine and Radiation Therapy
• Volume: Volume 53, Number 8
• Publisher: Society of Nuclear Medicine | 2012-08, Pages 1277-1283
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.2967/jnumed.111.102236
• Subjects: Health Sciences, General; Health Sciences, Radiology; Chemistry, General
• Keywords: Technetium-99m (99mTc); Tricarbonyl; Kidney; Renal radiopharmaceuticals; 131I-ortho-iodohippurate; 99mTc(CO)3(ASMA)

Abstract

In an ongoing effort to develop a renal tracer with pharmacokinetic properties comparable to PAH and superior to those of both 99mTc-MAG3 and 131I-OIH, we evaluated a new renal tricarbonyl radiotracer based on the aspartic-N-monoacetic acid ligand, 99mTc(CO)3(ASMA). The ASMA ligand features two 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 HPLC. 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 PBS buffer pH 7.4 and in challenge studies with cysteine and histidine. 99mTc(CO)3(ASMA) metabolites in urine were analyzed by HPLC. Results Both 99mTc(CO)3(ASMA) preparations had > 99% radiochemical purity and were stable in PBS buffer pH 7.4 for 24 h. Challenge studies on both revealed no significant displacement of the ligand. In normal rats, % injected dose in urine at 10 and 60 min for both preparations averaged 103% and 106% that of 131I-OIH, respectively. 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) and was better retained in the blood (P < 0.05) than 131I-OIH. 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.