@article{d85748d1fc27498bb017a5d8a9d95c6b,
title = "Fluorine-18 (18F)-labeled retinoid x receptor (RXR) partial agonist whose tissue transferability is affected by other RXR ligands",
abstract = "Bexarotene (1), a retinoid X receptor (RXR) agonist approved for the treatment of cutaneous T cell lymphoma (CTCL), was reported to migrate into baboon brain based on findings obtained by positron emission tomography (PET) with a 11C-labeled tracer. However, co-administration of non-radioactive 1 had no effect on the distribution of [11C]1, probably due to non-specific binding of 1 as a result of its high lipophilicity. Here, we report a fluorine-18 (18F)-labeled PET tracer [18F]6 derived from RXR partial agonist CBt-PMN (2), which has lower lipophilicity and weaker RXR-binding ability than [11C]1. The concomitant administration of 1 or 2 with [18F]6 with resulted in decreased accumulation of [18F]6 in liver, together with increased brain uptake and increased accumulation in kidney and muscle, as visualized by PET. A plausible explanation of these findings is the inhibition of [18F]6 uptake into the liver by concomitantly administered 1 or 2, leading to an increase in blood concentration of [18F]6 followed by increased accumulation in other tissues.",
keywords = "F, Nuclear receptors, PET imaging, Pharmacokinetics, RXR, Retinoids",
author = "Yuta Takamura and O. Shibahara and Masaki Watanabe and Michiko Fujihara and S. Yamada and Masaru Akehi and Takanori Sasaki and Hiroyuki Hirano and Hiroki Kakuta",
note = "Funding Information: The authors are grateful to the Division of Instrumental Analysis, Okayama University for the NMR and MS measurements. This work was partially supported by a subsidy to promote science and technology in prefectures where nuclear and other power plants are located (to H.K.) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, a Grant-in-Aid for the COE projects by MEXT, Japan, titled “Center of excellence for molecular and gene targeting therapies with microdose molecular imaging modalities” (to H.K.), and Takeda Science Foundation (to H.K.). and The Tokyo Biochemical Research Foundation (TBRF) (to H.K.). H.K. conceived and designed the project. Y.T. and O.S. synthesized compounds. Y.T. O.S. M.W. and H.K. performed LRMS and HRMS. Y.T. O.S. and M.W. performed LC-MS. Y.T. O.S. M.A. H.H. and H.K. synthesized PET tracer. Y.T. M.A. and H.K. obtained LogD data. Y.T. O.S. M.A. T.S. and H.K. performed PET scanning and ARG. Y.T. O.S. and T.S. analyzed PET data. The manuscript was written by Y.T. O.S. and H.K. All authors analyzed and discussed the data. This research was partially performed in collaboration with AIBIOS Co. Ltd. Michiko Fujihara was an employee of AIBOS. No other author reports any potential conflict of interest relevant to this article. Funding Information: The authors are grateful to the Division of Instrumental Analysis, Okayama University for the NMR and MS measurements. This work was partially supported by a subsidy to promote science and technology in prefectures where nuclear and other power plants are located (to H.K.) from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan, a Grant-in-Aid for the COE projects by MEXT, Japan, titled ?Center of excellence for molecular and gene targeting therapies with microdose molecular imaging modalities? (to H.K.), and Takeda Science Foundation (to H.K.). and The Tokyo Biochemical Research Foundation (TBRF) (to H.K.). H.K. conceived and designed the project. Y.T. and O.S. synthesized compounds. Y.T. O.S. M.W. and H.K. performed LRMS and HRMS. Y.T. O.S. and M.W. performed LC-MS. Y.T. O.S. M.A. H.H. and H.K. synthesized PET tracer. Y.T. M.A. and H.K. obtained LogD data. Y.T. O.S. M.A. T.S. and H.K. performed PET scanning and ARG. Y.T. O.S. and T.S. analyzed PET data. The manuscript was written by Y.T. O.S. and H.K. All authors analyzed and discussed the data. This research was partially performed in collaboration with AIBIOS Co. Ltd. Michiko Fujihara was an employee of AIBOS. No other author reports any potential conflict of interest relevant to this article. Funding Information: This work was partially supported by a subsidy to promote science and technology in prefectures where nuclear and other power plants are located (to H.K.) from the Ministry of Education, Culture, Sports, Science, and Technology ( MEXT ) of Japan, a Grant-in-Aid for the COE projects by MEXT, Japan, titled “Center of excellence for molecular and gene targeting therapies with microdose molecular imaging modalities” (to H.K.), and Takeda Science Foundation (to H.K.). and The Tokyo Biochemical Research Foundation (TBRF) (to H.K.). Publisher Copyright: {\textcopyright} 2019",
year = "2019",
month = jul,
day = "15",
doi = "10.1016/j.bmc.2019.05.045",
language = "English",
volume = "27",
pages = "3128--3134",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "14",
}