Development of F-Labeled Radiotracers for PET Imaging of the Adenosine A Receptor: Synthesis, Radiolabeling and Preliminary Biological Evaluation.

The adenosine A receptor (AR) represents a potential therapeutic target for neurodegenerative diseases. Aiming at the development of a positron emission tomography (PET) radiotracer to monitor changes of receptor density and/or occupancy during the AR-tailored therapy, we designed a library of fluorinated analogs based on a recently published lead compound (). Among those, the highly affine 4-fluorobenzyl derivate (; (AR) = 5.3 nM) and the 2-fluorobenzyl derivate (; (AR) = 2.1 nM) were chosen for F-labeling via an alcohol-enhanced copper-mediated procedure starting from the corresponding boronic acid pinacol ester precursors. Investigations of the metabolic stability of [F] and [18F] in CD-1 mice by radio-HPLC analysis revealed parent fractions of more than 76% of total activity in the brain. Specific binding of [F] on mice brain slices was demonstrated by in vitro autoradiography. In vivo PET/magnetic resonance imaging (MRI) studies in CD-1 mice revealed a reasonable high initial brain uptake for both radiotracers, followed by a fast clearance.