Synthesis of PET probe O-[(3-[C]methyl)benzyl]guanine by Pd-mediated rapid C-[C]methylation toward imaging DNA repair protein O-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

Journal: Bioorganic & medicinal chemistry letters 2017;27(9):1892-1896

PMID: 28363750

Free Full Text on Nagoya University Repository - Access Free Full Text View on PubMed

Abstract

O-Benzylguanine (O-BG) is a substrate of O-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 C-labeled O-[(3-methyl)benzyl]guanine ([C]mMeBG) as a positron emission tomography probe. Thus, a mixed amine-protected stannyl precursor, N-(tert-butoxycarbonyl)-O-[3-(tributylstannyl)benzyl]-N-(trifluoroacetyl)guanine, was subjected to rapid C-[C]methylation under [C]CHI/[Pd(dba)]/P(o-CHCH)/CuCl/KCO in NMP, followed by quick deprotection with LiOH/HO, giving [C]mMeBG with total radioactivity of 1.34GBq and ≥99% radiochemical and chemical purities.

Address: Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan. Electronic address: [email protected].; 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.; Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.; Division of Regeneration and Advanced Medical Science, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.; Department of Food and Nutritional Science, College of Bioscience and Biotechnology, Chubu University, Matsumoto-cho, Kasugai, Aichi 487-8501, Japan.; Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. Electronic address: [email protected].; 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: [email protected].

DOI: 10.1016/j.bmcl.2017.03.045

Link outs

Free resources

Full Text Sources:

http://hdl.handle.net/2237/26868

Medical:

https://medlineplus.gov/braintumors.html

Other Literature Sources:

Research Materials:

https://antibodies.cancer.gov/detail/CPTC-MGMT-1

Subscription / membership required

Full Text Sources:

https://linkinghub.elsevier.com/retrieve/pii/S0960...

MeSH Terms: Brain, Brain Neoplasms, Carbon Radioisotopes, Glioblastoma, Guanine, Humans, Methylation, O(6)-Methylguanine-DNA Methyltransferase, Palladium, Positron-Emission Tomography