title: Benzyl [(11)C]Hippurate as an Agent for Measuring the Activities of Organic Anion Transporter 3 in the Brain and Multidrug Resistance-Associated Protein 4 in the Heart of Mice.
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.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.|Division of Imaging Sciences and Biomedical Engineering, King's College London , Fourth Floor Lambeth Wing, St. Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, United Kingdom.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Okada
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.|SHI Accelerater Service Co. Ltd. , 5-9-1 Kitashinagawa, Shinagawa-ku, Tokyo 141-8686, Japan.
authors.forename: Masanao
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.|Preeminent Medical Photonics Education Research Center, Hamamatsu University School of Medicine , 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Suzuki
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Wakizaka
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Joji
authors.initials: J
authors.lastname: Yui
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Fukumura
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London , Fourth Floor Lambeth Wing, St. Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, United Kingdom.
authors.forename: Antony D
authors.initials: AD
authors.lastname: Gee
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences , 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Zhang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D006321:Heart; D006626:Hippurates / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000172:deficiency / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000172:deficiency / Q000378:metabolism*; D049268:Positron-Emission Tomography; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D006626:Hippurates; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D029362:Organic Anion Transporters, Sodium-Independent; C489540:Abcc4 protein, mouse; C114338:organic anion transport protein 3; C030514:hippuric acid