Synthesis and pre-clinical evaluation of a potential radiotracer for PET imaging of the dopamine D3 receptor

There is considerable interest in using positron emission tomography (PET) imaging to understand the function of dopamine D 3 receptors. Due to high sequence homology with D 2 receptors, development of D 3 -selective PET radiotracers has been challenging. In an effort to overcome this issue, we report the radiosynthesis of a new selective D 3 ligand with carbon-11 ( [ 11 C] 1 ), and its initial preclincial evaluation as a potential PET radiotracer for in vivo imaging of D 3 receptors. [ 11 C] 1 was prepared via [ 11 C]CO 2 fixation in 0.1% non-corrected radiochemical yield, good radiochemical purity (>95%) and high specific activity (>2000 Ci mmol −1 ). [ 11 C] 1 exhibited specific binding to D 3 receptors using ex vivo autoradiography experiments with rat brain, but only 14-fold selectivity over D 2 receptors which is lower than the 1400-fold value reported previously for cell studies. Rodent PET imaging revealed reasonable uptake of the radiotracer in areas of the brain known to be rich in D 3 receptors. There is considerable interest in using PET imaging to quantify dopamine D 3 receptors. We report a new D 3 -selective radioligand, and describe preclincial evaluation in rodent using ex vivo autoradiography and in vivo PET imaging.