AI Article Synopsis
- This study focuses on two transport proteins, MRP4 and OAT3, that help remove organic substances from the brain and heart.
- Researchers developed a radioactive probe using a specific compound called benzyl [(11)C]hippurate to measure how well these transporters are working.
- Tests showed that this probe effectively indicates transporter activity in mice, as it retained more radioactivity in mice lacking OAT3 and MRP4, making it a useful tool for studying these proteins.
Article Abstract
Multidrug resistance-associated protein 4 (MRP4) and organic anion transporter 3 (OAT3) mediate the efflux of organic anions from the brain and heart. In this study, we have developed a probe for estimating the activity of these transporters in these tissues using positron emission tomography. Several (11)C-labeled hippuric acid ester derivatives were screened with the expectation that they would be hydrolyzed in situ to form the corresponding (11)C-labeled organic acids in target tissues. Among the compounds screened, benzyl [(11)C]hippurate showed favorable hydrolysis rates and uptake properties in the target tissues of mice. Subsequent evaluation using transporter knockout mice revealed that radioactivity was retained in the brain and heart of Oat3(-/-) and Mrp4(-/-) mice, respectively, compared with that of control mice after the intravenous administration of benzyl [(11)C]hippurate. Benzyl [(11)C]hippurate could therefore be used as a probe for estimating the activities of OAT3 and MRP4 in mouse brain and heart, respectively.
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| http://dx.doi.org/10.1021/acs.jmedchem.6b00454 | DOI Listing |
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