Radiolabeled guanine derivatives for the in vivo mapping of O-6-alkylguanine-DNA alkyltransferase: 6-(4-[F-18]fluoro-benzyloxy)-9H-purin-2-ylamine and 6-(3-[I-131]iodo-benzyloxy)-9H-purin-2-ylamine

Two radiolabeled analogues of 6-benzyloxy-9H-purin-2-ylamine (O-6-benzylgua nine; BG) potentially useful in the in vivo mapping of O-6-alkylguanine-DNA alkyltransferase (AGT) were synthesized. Fluorine-18 labeling of the known 6-(4-fluoro-benzyloxy)-9H-purin-2-ylamine (FBG; 6) was accomplished by the condensation of 4-[F-18]fluorobenzyl alcohol with 2-aminopurin-6-yltrimeth ylammonium chloride (4) or 2-amino-6-chloropurine in average decay-correcte d radiochemical yields of 40 and 25%, respectively. Unlabeled 6-(3-iodo-ben zyloxy)-9H-purin-2-ylamine (IBG; 7) was prepared from 4 and 3-iodobenzyl al cohol. Radioiodination of 9, prepared from 7 in two steps, and subsequent d eprotect ion gave [I-131]7 in about 70% overall radiochemical yield. The IC 50 values for the inactivation of AGT from CHO cells transfected with pCMV- AGT were 15 nM for IBG and 50 nM for FBG. The binding of [F-18]6 and [I-131 ]7 to purified AGT was specific and saturable with both exhibiting similar IC50 values (5-6 muM).