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 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 11 C-labeled O 6 -[(3-methyl)benzyl]guanine ([ 11 C] m MeBG) as a positron emission tomography probe. Thus, a mixed amine-protected stannyl precursor, N 9 -( tert -butoxycarbonyl)- O 6 -[3-(tributylstannyl)benzyl]- N 2 -(trifluoroacetyl)guanine, was subjected to rapid C -[ 11 C]methylation under [ 11 C]CH 3 I/[Pd 2 (dba) 3 ]/P( o -CH 3 C 6 H 4 ) 3 /CuCl/K 2 CO 3 in NMP, followed by quick deprotection with LiOH/H 2 O, giving [ 11 C] m MeBG with total radioactivity of 1.34 GBq and ≥99% radiochemical and chemical purities.