Expanding tracer space for positron emission tomography with high molar activity 18F-labeled α,α-difluoromethylalkanes

Positron emission tomography (PET) is an advanced biomedical imaging modality that relies on well-designed radiotracers to report on specific protein targets and processes occurring in living animals and humans. Cyclotron-produced short-lived fluorine-18 (t1/2 = 109.8 min) is widely used to radiolabel tracers for PET. Herein we aim to expand the chemical space available for PET tracer development to include structures with 18F-labeled alpha,alpha-difluoromethylalkyl groups. We report an efficient and broad-scope method for labeling such groups with high molar activities based on a single-step radiofluorination of alpha-bromo-alpha-fluoroalkanes. The method is applicable to bioactive compounds and drug-like molecules, and is readily automated for radiotracer production. The unique physical and biochemical features of the alpha,alpha-difluoromethyl group can now be exploited in the design of new PET tracers.