title: Biodistribution and renal excretion of isomers of the cationic tracer, (99m)Tc 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 (131)I 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, (99m)Tc labeled diaminocyclohexane ((99m)Tc DACH), has a clearance of 80% of OIH in mice but its clearance in humans is relatively low, only 30% of OIH. The (99m)Tc 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 (99m)Tc renal tracers have been shown to have widely different clearances, the biodistribution and urine excretion of the (99m)Tc 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 (99m)Tc DACH isomers may be a significantly better renal tracer than the others. The red cell binding of (99m)Tc +/- 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 (99m)Tc DACH isomers will have a substantially higher clearance in humans than the form of (99m)Tc DACH originally tested. Development of alternative cationic renal tracers is warranted.
authors.affiliation: Department of Radiology, Emory University, 1364 Clifton Road NE, Atlanta, GA 30322, USA. ataylor@emory.edu
authors.forename: A
authors.initials: A
authors.lastname: Taylor
authors.forename: L
authors.initials: L
authors.lastname: Hansen
authors.forename: L G
authors.initials: LG
authors.lastname: Marzilli
mesh_terms: D000818:Animals; D003514:Cyclohexylamines / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D007668:Kidney / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D019275:Radiopharmaceuticals / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D003514:Cyclohexylamines; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C084614:technetium Tc 99m diaminocyclohexane