A Potential Dubin-Johnson Syndrome Imaging Agent: Synthesis, Biodistribution, and MicroPET Imaging

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 (5) was prepared and evaluated for potential as a diagnostic tool...

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Main Authors: Jeongsoo Yoo, David E. Reichert, Joonyoung Kim, Carolyn J. Anderson, Michael J. Welch
Format: Article
Language:English
Published: SAGE Publishing 2005-01-01
Series:Molecular Imaging
Online Access:https://doi.org/10.1162/15353500200504160
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author Jeongsoo Yoo
David E. Reichert
Joonyoung Kim
Carolyn J. Anderson
Michael J. Welch
author_facet Jeongsoo Yoo
David E. Reichert
Joonyoung Kim
Carolyn J. Anderson
Michael J. Welch
author_sort Jeongsoo Yoo
collection DOAJ
description 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 (5) was prepared and evaluated for potential as a diagnostic tool for DJS. The prepared ligand was labeled with 64 Cu 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 − ) rats. In normal rats, the radioactive copper complex was cleared quickly from the body exclusively through the hepatic pathway. The 64 Cu complex was taken up rapidly by the liver and quickly excreted into the small intestine and then the upper large intestine, whereas < 1% ID/organ was found in the kidney at all time points post injection. Whereas 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. This study strongly suggests that cMOAT is involved in excretion of 64 Cu-5. The significant difference between the biodistribution data and microPET images of the normal and TR − rats demonstrates that this new 64 Cu complex may allow noninvasive diagnosis of DJS in humans.
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spelling doaj-art-9c42f23fa21c48fd98305559650837ae2025-01-02T22:38:05ZengSAGE PublishingMolecular Imaging1536-01212005-01-01410.1162/1535350020050416010.1162_15353500200504160A Potential Dubin-Johnson Syndrome Imaging Agent: Synthesis, Biodistribution, and MicroPET ImagingJeongsoo YooDavid E. ReichertJoonyoung KimCarolyn J. AndersonMichael J. WelchDubin-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 (5) was prepared and evaluated for potential as a diagnostic tool for DJS. The prepared ligand was labeled with 64 Cu 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 − ) rats. In normal rats, the radioactive copper complex was cleared quickly from the body exclusively through the hepatic pathway. The 64 Cu complex was taken up rapidly by the liver and quickly excreted into the small intestine and then the upper large intestine, whereas < 1% ID/organ was found in the kidney at all time points post injection. Whereas 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. This study strongly suggests that cMOAT is involved in excretion of 64 Cu-5. The significant difference between the biodistribution data and microPET images of the normal and TR − rats demonstrates that this new 64 Cu complex may allow noninvasive diagnosis of DJS in humans.https://doi.org/10.1162/15353500200504160
spellingShingle Jeongsoo Yoo
David E. Reichert
Joonyoung Kim
Carolyn J. Anderson
Michael J. Welch
A Potential Dubin-Johnson Syndrome Imaging Agent: Synthesis, Biodistribution, and MicroPET Imaging
Molecular Imaging
title A Potential Dubin-Johnson Syndrome Imaging Agent: Synthesis, Biodistribution, and MicroPET Imaging
title_full A Potential Dubin-Johnson Syndrome Imaging Agent: Synthesis, Biodistribution, and MicroPET Imaging
title_fullStr A Potential Dubin-Johnson Syndrome Imaging Agent: Synthesis, Biodistribution, and MicroPET Imaging
title_full_unstemmed A Potential Dubin-Johnson Syndrome Imaging Agent: Synthesis, Biodistribution, and MicroPET Imaging
title_short A Potential Dubin-Johnson Syndrome Imaging Agent: Synthesis, Biodistribution, and MicroPET Imaging
title_sort potential dubin johnson syndrome imaging agent synthesis biodistribution and micropet imaging
url https://doi.org/10.1162/15353500200504160
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