Synthesis of PET probe O-6-[(3-[C-11]methyl)benzyl]guanine by Pd-0-mediated rapid C-[C-11]methylation toward imaging DNA repair protein O-6-methylguanine-DNA methyltransferase in glioblastoma

摘要

O-6-Benzylguanine (O-6-BG) is a substrate of O-6-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-11-labeled O-6-[(3-methyl)benzyl]guanine ([C-11]rnMeBG) as a positron emission tomography probe. Thus, a mixed amine-protected stannyl precursor, N-9-(tert-butoxycarbony1)-O-6-[3-(tributylstannyl)benzyl]-N-2-(trifluoroacetyl)guanine, was subjected to rapid C-[C-11]methylation under [C-11]CH3/[Pd-2(dba)(3)]/P(o-CH3C6H4)(3)/CuCl/K2CO3 in NMP, followed by quick deprotection with LiOH/H2O, giving [C-11]mMeBG with total radioactivity of 1.34 GBq and >= 99% radiochemical and chemical purities. (C) 2017 Elsevier Ltd. All rights reserved.