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
; 27(9): 1892-1896, 2017 05 01.
Article
em En
| MEDLINE
| ID: mdl-28363750
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.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Neoplasias Encefálicas
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Radioisótopos de Carbono
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Glioblastoma
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O(6)-Metilguanina-DNA Metiltransferase
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Tomografia por Emissão de Pósitrons
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Guanina
Limite:
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article