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

摘要

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.Methodsrac-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.