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

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 < 0.05) and had less excretion into the bowel than did ¹³¹I-OIH (P < 0.05).

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