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

Hiroko Koyama; Hiroshi Ikenuma; Hiroshi Toda; Goro Kondo; Masaki Hirano; Masaya Kato; Junichiro Abe; Takashi Yamada; Toshihiko Wakabayashi; Kengo Ito; Atsushi Natsume; Masaaki Suzuki

doi:10.1016/j.bmcl.2017.03.045

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

Bioorg Med Chem Lett. 2017 May 1;27(9):1892-1896. doi: 10.1016/j.bmcl.2017.03.045. Epub 2017 Mar 18.

Authors

Affiliations

¹ 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.
² 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.
³ Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
⁴ Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
⁵ Department of Food and Nutritional Science, College of Bioscience and Biotechnology, Chubu University, Matsumoto-cho, Kasugai, Aichi 487-8501, Japan.
⁶ 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.
⁷ 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.

PMID: 28363750
DOI: 10.1016/j.bmcl.2017.03.045

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 synthesized ¹¹C-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/K₂CO₃ in NMP, followed by quick deprotection with LiOH/H₂O, giving [¹¹C]mMeBG with total radioactivity of 1.34GBq and ≥99% radiochemical and chemical purities.

Keywords: (11)C labeling; Brain cancer imaging; O(6)-Benzylguanine; Positron emission tomography probe; Rapid C-[(11)C]methylation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain / diagnostic imaging*
Brain Neoplasms / diagnostic imaging*
Carbon Radioisotopes / chemistry*
Carbon Radioisotopes / metabolism
Glioblastoma / diagnostic imaging*
Guanine / analogs & derivatives*
Guanine / chemistry
Guanine / metabolism
Humans
Methylation
O(6)-Methylguanine-DNA Methyltransferase / analysis*
O(6)-Methylguanine-DNA Methyltransferase / metabolism
Palladium / chemistry
Positron-Emission Tomography / methods*

Substances

Carbon Radioisotopes
O(6)-benzylguanine
Palladium
Guanine
O(6)-Methylguanine-DNA Methyltransferase