Synthesis of radiolabeled O 6 ‐benzylguanine derivatives as new potential PET tumor imaging agents for the DNA repair protein O 6 ‐alkylguanine‐DNA alkyltransferase

Novel radiolabeled O 6 ‐benzylguanine derivatives, 2‐amino‐6‐O‐[ 11 C]‐[(methoxymethyl)benzyloxy]‐9‐benzyl purines ([ 11 C] p ‐O 6 ‐AMBP, 1a ; [ 11 C] m ‐O 6 ‐AMBP, 1b ; [ 11 C] o ‐O 6 ‐AMBP, 1c ), have been synthesized for evaluation as new potential positron emission tomography (PET) tumor imaging agents for the DNA repair protein, O 6 ‐alkylguanine‐DNA alkyltransferase (AGT). The appropriate precursors for radiolabeling were obtained in three steps from starting material 2‐amino‐6‐chloropurine with moderate to excellent chemical yields. Tracers were prepared by O‐[ 11 C]methylation of hydroxymethyl precursors using [ 11 C]methyl triflate. Pure target compounds were isolated by solid‐phase extraction (SPE) purification procedure in 45–60% radiochemical yields (decay corrected to the end of bombardment), and a synthesis time of 20–25min. Copyright © 2002 John Wiley & Sons, Ltd.