Biodistribution and renal excretion of isomers of the cationic tracer, Tc-99m diaminocyclohexane (DACH) biodistribution of cationic renal tracers

The buildup of organic anions in the plasma in the uremic state can competi tively inhibit the tubular extraction of para-aminohippurate I-131 ortho-io dohippurate (OIH) and lead to spuriously low measurements of effective rena l plasma flow (ERPF). This problem can be circumvented by the use of cation ic tracers. The cationic renal tracer, Tc-99m labeled diaminocyclohexane (T c-99m DACH), has a clearance of 80% of OIH in mice but its clearance in hum ans is relatively low, only 30% of OIH. The Tc-99m DACH isomer(s) used in p rior studies, however, was not clearly defined and may have consisted of a single isomer or a combination of isomers. Since the anionic isomers of som e Tc-99m renal tracers have been shown to have widely different clearances, the biodistribution and urine excretion of the Tc-99m cis-, trans-S,S, tra ns-R,R and +/- trans-DACH isomers were compared in Sprague-Dawley rats at 1 0 minutes and 60 minutes postinjection to determine if one of the Tc-99m DA CH isomers may be a significantly better renal tracer than the others. The red cell binding of Tc-99m +/- trans-DACH was also determined. All of the i somers showed a high degree of specificity for the kidney with minimal secr etion into the gastrointestinal tract. Urine excretion of the 4 tracers, ho wever, 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 pote ntial to provide a more accurate measurement of ERPF than anionic tracers. Based on the animal data, however, it is unlikely that any of the Tc-99m DA CH isomers will have a substantially higher clearance in humans than the fo rm of Tc-99m DACH originally tested. Development of alternative cationic re nal tracers is warranted. (C) 2001 Elsevier Science Inc. All rights reserve d.