Reductive Amination with [¹¹C]Formaldehyde: A Versatile Approach to Radiomethylation of Amines

Abstract

Carbon-11 radiolabeled amines constitute a very important class of radioligands that are widely used for positron emission tomography (PET) imaging. Radiolabeling of amines is often achieved through radiomethylation using [ 11 C]CH 3 I or [ 11 C]CH 3 OTf under basic conditions in a strictly anhydrous environment. Functional groups such as hydroxyl and carboxyl groups that are often present in the molecules are normally base sensitive and require protection and deprotection, which substantially prolongs and complicates the radiolabeling process. Here we report a versatile approach to a series of C-11 radiolabeled amines prepared through reductive amination using [ 11 C]formaldehyde. Using a variety of substrates bearing different functional groups, we demonstrate the general utility of this method. In contrast to conventional radiomethylation methods, the reductive amination using [ 11 C]formaldehyde can be carried out in an aqueous environment relatively quickly without the need of protection of base-sensitive functional groups.