Initial Evaluation of 99mTc(CO)3(ASMA) as a Renal Tracer in Healthy Human Volunteers

Lipowska, Malgorzata; Klenc, Jeffrey; Folks, Russell D; Taylor, Andrew T

Abstract

PURPOSE
Preclinical studies in rats showed that two of 99mTc(CO)3(ASMA) isomers (rac- and L-ASMA) had pharmacokinetic properties equivalent to that of 131I-OIH, the radiopharmaceutical standard for the measurement of effective renal plasma flow. The aim of this study was to evaluate the pharmacokinetics of 99mTc(CO)3(ASMA) isomers in healthy human subjects.
METHODS
Three ASMA ligands (rac-, L- and D-ASMA) were labeled with 99mTc(CO)3using an IsoLink kit (Covidien), and each formed 99mTc(CO)3(ASMA) tracer was co-injected with 131I-OIH into healthy human subjects followed by sequential imaging, plasma clearance measurements and timed urine collection. Plasma protein binding, red cell uptake and percent injected dose in the urine were determined. Urine from each group of volunteers was analyzed for metabolites by HPLC.
RESULTS
Image quality was excellent with all three agents. Each 99mTc(CO)3(ASMA) preparation was excreted un-changed in the urine. The plasma clearance ratio (99mTc(CO)3(ASMA)/131I-OIH) was 81+/-3% for D-ASMA compared to only 20+/-4% for L-ASMA and 37+/-7% for rac-ASMA; the 81% clearance ratio for D-ASMA isomer is still~30% higher than the 99mTc-MAG3/131I-OIH clearance ratio (~50-60%). Red cell uptake was similar for all three tracers (6-9%), and all tracers had a relatively rapid renal excretion; at 3 h, the 99mTc(CO)3(ASMA)/131I-OIH urine ratio was 100+/-3% for D-ASMA, 80+/-2% for L-ASMA and 88+/-1% for rac-ASMA.
CONCLUSION
The renal excretion characteristics of 99mTc(CO)3(D-ASMA) in humans are superior to those of the other two 99mTc(CO)3(ASMA) isomers studied, but are still inferior to 131I-OIH, even though there was no difference in the clearance of two of 99mTc(CO)3(ASMA) isomers and 131I-OIH in rats. The work described here demonstrates the sensitivity in in vivo biological behavior of 99mTc(CO)3(ASMA) isomers to their subtle structural differences.