title: Synthesis of (11)C-labeled retinoic acid, [(11)C]ATRA, via an alkenylboron precursor by Pd(0)-mediated rapid C-[(11)C]methylation.
abstract: Retinoids are a class of chemical compounds which include both natural dietary vitamin A (retinol) metabolites and active synthetic analogs. Both experimental and clinical studies have revealed that retinoids regulate a wide variety of essential biological processes. In this study, we synthesized (11)C-labeled all-trans-retinoic acid (ATRA), the most potent biologically active metabolite of retinol and used in the treatment of acute promyelocytic leukemia. The synthesis of (11)C-labeled ATRA was accomplished by a combination of rapid Pd(0)-mediated C-[(11)C]methylation of the corresponding pinacol borate precursor prepared by 8 steps and hydrolysis. [(11)C]ATRA will prove useful as a PET imaging agent, particularly for elucidating the improved therapeutic activity of ATRA (natural retinoid) for acute promyelocytic leukemia by comparing with the corresponding PET probe [(11)C]Tamibarotene (artificial retinoid).
authors.affiliation: Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology Center, 35, Gengo Morioka-cho, Obu-shi, Aichi 474-8511, Japan; RIKEN Center for Molecular Imaging Science (CMIS), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan. Electronic address: suzukims@ncgg.go.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: RIKEN Center for Molecular Imaging Science (CMIS), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Misato
authors.initials: M
authors.lastname: Takashima-Hirano
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Science (NIRS), 4-9-1 Anagawa, Inage-ku, Chiba 263-8555, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Ishii
authors.affiliation: Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1184, Japan.
authors.forename: Chika
authors.initials: C
authors.lastname: Watanabe
authors.affiliation: Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1184, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Sumi
authors.affiliation: Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1184, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Koyama
authors.affiliation: RIKEN Center for Molecular Imaging Science (CMIS), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan; RIKEN Center for Life Science Technologies (CLST), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Doi
mesh_terms: D000475:Alkenes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001896:Boron Compounds / Q000737:chemistry*; D002247:Carbon Isotopes; D002384:Catalysis; D003287:Contrast Media; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D008745:Methylation; D010165:Palladium / Q000737:chemistry*; D049268:Positron-Emission Tomography; D014212:Tretinoin / Q000138:chemical synthesis* / Q000627:therapeutic use
chemical_list: D000475:Alkenes; D000970:Antineoplastic Agents; D001896:Boron Compounds; D002247:Carbon Isotopes; D003287:Contrast Media; D014212:Tretinoin; D010165:Palladium
keywords: (11)C labeling; PET; Retinoids