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Synthesis and in vivo evaluation of cyclen-based Cu(II) complex as a diagnostic agent for Dubin-Johnson syndrome

Submission Date :
8 / 19 / 2005 , 15 : 38 : 35
Abstract Number :
Presenting Type:
Oral Presentation
Presenting Area :
Authors :
유정수, Michael J. Welch1
경북대학교 분자의학과,
1Washington University School of Medicine,
Assigned Code :
토21I7구 Assigend Code Guideline
Presenting Time :
토 11시 : 20분
Dubin-Johnson syndrome (DJS) is caused by a deficiency of the human canalicular multispecific organic anion transporter (cMOAT). A new lipophilic copper-64 complex of 1,4,7-tris(carboxymethyl)-10-(tetradecyl)-1,4,7,10-tetraazadodecane was prepared and evaluated for potential as a diagnostic tool for DJS. The prepared ligand was labeled with 64Cu-citrate in high radiochemical purity. In vivo uptake and clearance of the complex was determined through biodistribution studies using normal Sprague-Dawley rats and mutant cMOAT-deficient (TR-) Wistar rats. In normal rats, the radioactive copper complex was cleared quickly from the body exclusively through the hepatic pathway. While activity was accumulated continuously in the liver of TR- rats, it was not excreted into the small intestine. MicroPET studies of normal and TR- rats were consistent with biodistribution data and showed dramatically different images. The significant difference between the microPET images of the normal and TR- rats demonstrates that this new 64Cu complex may allow noninvasive diagnosis of DJS in humans.