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2015 Fiscal Year Final Research Report

Development of a PET probe for measuring the activity of multidrug resistance-associated protein 4 in the brain

Research Project

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Project/Area Number 24591826
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Radiation science
Research InstitutionNational Institute of Radiological Sciences

Principal Investigator

Kikuchi Tatsuya  国立研究開発法人放射線医学総合研究所, 分子イメージング研究センター, 主任研究員 (90392224)

Project Period (FY) 2012-04-01 – 2016-03-31
KeywordsPET / 多剤耐性関連タンパク質 / 有機アニオントランスポータ / 馬尿酸 / 脳 / 心臓
Outline of Final Research Achievements

The aim of this study was to develop a PET probe for measuring the activity of multidrug resistance-associated protein 4 (MRP4) in the brain. Several hippuric acid ester derivatives labeled with C-11 were synthesized and benzyl hippurate labeled with C-11 showed favorable hydrolysis rate and uptake properties in the brain of mice. Further evaluation using transporter knockout mice revealed that this compound was specifically hydrolyzed to form hippuric acid labeled with C-11 in vivo after the intravenous administration and the radioactive metabolite was retained in the brain and heart of Oat3 knockout mice and Mrp4 knockout mice, respectively, compared with control mice. Therefore, benzyl hippurate labeled with C-11 could be used as a probe for measuring the activities of OAT3 and MRP4 in mouse brain and heart, respectively.

Free Research Field

放射性医薬品科学

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Published: 2017-05-10  

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