Synthesis, characterization and in vivo biodistribution of 99mTc(CO)3-N-carboxymethyl-aspartic acid as a potential renal imaging tracer

345 Objectives In an ongoing effort to develop a renal tracer with pharmacokinetic properties superior to both those of 131I-OIH and the promising new 99mTc agent, 99mTc(CO)3-nitirilotriacetic acid [99mTc(CO)3(NTA)], we modified the aminopolycarboxylate ligand structure of NTA to produce N-carboxymethyl-aspartic acid (ASMA). ASMA has two carboxyl groups and an amine function available for the coordination of the {99mTc(CO)3}+ core as well as a dangling carboxylate to facilitate rapid renal clearance. Methods ASMA was labeled with 99mTc(CO)3 using an IsoLink kit (Covidien), isolated by HPLC, and evaluated in normal Sprague-Dawley rats at 10 min and 60 min (group A) and in rats with renal pedicle ligation at 60 min (group B). 131I-OIH was co-injected simultaneously as an internal control. Radiotracer stability was determined in PBS buffer pH 7.4 and a Re analogue was prepared. Results 99mTc(CO)3(ASMA) was obtained in almost quantitative yield with radiochemical purity >98%, and the complex was stable at PBS buffer pH 7.4 for 24h at 25 °C. NMR of the Re analogue showed the product was composed of diasteroisomers due to the chiral center in ASMA; however the 99mTc diasteroisomers could not be separated by preparative HPLC. In normal rats, %ID in the urine at 10 and 60 min was 106±6% and 106±0%, respectively, that of 131I-OIH; hepatic/gastrointestinal activity was minimal and less than 131I-OIH. In rats with renal pedicle ligation, 99mTc(CO)3(ASMA) was better retained in the blood (P Conclusions 99mTc(CO)3(ASMA) has pharmacokinetic properties in rats comparable to or superior to those of 131I-OIH. Human studies are warranted for further evaluation of 99mTc(CO)3(ASMA) as a potential renal imaging agent. Research Support NIH R37 DK3884