title: Synthesis of PET probe O6-[(3-[11C]methyl)benzyl]guanine by Pd0-mediated rapid C-[11C]methylation toward imaging DNA repair protein O6-methylguanine-DNA methyltransferase in glioblastoma.
abstract: O6-Benzylguanine (O6-BG) is a substrate of O6-methylguanine-DNA methyltransferase (MGMT), which is involved in drug resistance of chemotherapy in the majority of glioblastoma multiform. For clinical diagnosis, it is hoped that the MGMT expression level could be determined by a noninvasive method to understand the detailed biological properties of MGMT-specific tumors. We synthesized11C-labeled O6-[(3-methyl)benzyl]guanine ([11C]mMeBG) as a positron emission tomography probe. Thus, a mixed amine-protected stannyl precursor, N9-(tert-butoxycarbonyl)-O6-[3-(tributylstannyl)benzyl]-N2-(trifluoroacetyl)guanine, was subjected to rapid C-[11C]methylation under [11C]CH3I/[Pd2(dba)3]/P(o-CH3C6H4)3/CuCl/K2CO3in NMP, followed by quick deprotection with LiOH/H2O, giving [11C]mMeBG with total radioactivity of 1.34GBq and ≥99% radiochemical and chemical purities.
authors.affiliation: Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. Electronic address: hirokok@gifu-u.ac.jp.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Koyama
authors.affiliation: Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu-shi, Aichi 474-8511, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikenuma
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Toda
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Goro
authors.initials: G
authors.lastname: Kondo
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hirano
authors.affiliation: Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu-shi, Aichi 474-8511, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Abe
authors.affiliation: Department of Food and Nutritional Science, College of Bioscience and Biotechnology, Chubu University, Matsumoto-cho, Kasugai, Aichi 487-8501, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Wakabayashi
authors.affiliation: Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu-shi, Aichi 474-8511, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Ito
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: anatsume@med.nagoya-u.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Natsume
authors.affiliation: Department of Clinical and Experimental Neuroimaging, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu-shi, Aichi 474-8511, Japan. Electronic address: suzukims@ncgg.go.jp.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes / Q000737:chemistry* / Q000378:metabolism; D005909:Glioblastoma / Q000000981:diagnostic imaging*; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008745:Methylation; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000032:analysis* / Q000378:metabolism; D010165:Palladium / Q000737:chemistry; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D002250:Carbon Radioisotopes; C064976:O(6)-benzylguanine; D010165:Palladium; D006147:Guanine; D019853:O(6)-Methylguanine-DNA Methyltransferase
keywords: (11)C labeling; Brain cancer imaging; O(6)-Benzylguanine; Positron emission tomography probe; Rapid C-[(11)C]methylation