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The adenosine A_2A receptor (A_2AR) 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 A_2AR-tailored therapy, we designed a library of fluorinated analogs based on a recently published lead compound (<b>PPY</b>). Among those, the highly affine 4-fluorobenzyl derivate (<b>PPY1</b>; <i>K</i>_i(<i>h</i>A_2AR) = 5.3 nM) and the 2-fluorobenzyl derivate (<b>PPY2</b>; <i>K</i>_i(<i>h</i>A_2AR) = 2.1 nM) were chosen for ¹⁸F-labeling via an alcohol-enhanced copper-mediated procedure starting from the corresponding boronic acid pinacol ester precursors. Investigations of the metabolic stability of [¹⁸F]<b>PPY1</b> and [18F]<b>PPY2</b> in CD-1 mice by radio-HPLC analysis revealed parent fractions of more than 76% of total activity in the brain. Specific binding of [¹⁸F]<b>PPY2</b> 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.