Biodistribution and renal excretion of isomers of the cationic tracer, 99mTc diaminocyclohexane (DACH) : Biodistribution of cationic renal tracers

Abstract

The buildup of organic anions in the plasma in the uremic state can competitively inhibit the tubular extraction of para-aminohippurate or 131I ortho-iodohippurate (OIH) and lead to spuriously low measurements of effective renal plasma flow (ERPF). This problem can be circumvented by the use of cationic tracers. The cationic renal tracer, 99mTc labeled diaminocyclohexane ( 99mTc DACH), has a clearance of 80% of OIH in mice but its clearance in humans is relatively low, only 30% of OIH. The 99mTc DACH isomer(s) used in prior studies, however, was not clearly defined and may have consisted of a single isomer or a combination of isomers. Since the anionic isomers of some 99mTc renal tracers have been shown to have widely different clearances, the biodistribution and urine excretion of the 99mTc cis-, trans-S,S, trans-R,R and ± trans-DACH isomers were compared in Sprague-Dawley rats at 10 minutes and 60 minutes postinjection to determine if one of the 99mTc DACH isomers may be a significantly better renal tracer than the others. The red cell binding of 99mTc ± trans-DACH was also determined. All of the isomers showed a high degree of specificity for the kidney with minimal secretion into the gastrointestinal tract. Urine excretion of the 4 tracers, however, was only 38–48% that of OIH at 10 minutes and 66–84% that of OIH at 60 minutes. Red cell binding was 6.9%. Cationic renal tracers have the potential to provide a more accurate measurement of ERPF than anionic tracers. Based on the animal data, however, it is unlikely that any of the 99mTc DACH isomers will have a substantially higher clearance in humans than the form of 99mTc DACH originally tested. Development of alternative cationic renal tracers is warranted.