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 D3 receptors. Due to high sequence homology with D2 receptors, development of D3-selective PET radiotracers has been challenging. In an effort to overcome this issue, we report the radiosynthesis of a new selective D3 ligand with carbon-11 ([11C]1 ), and its initial preclincial evaluation as a potential PET radiotracer for in vivo imaging of D3 receptors. [11C]1 was prepared via [11C]CO2 fixation in 0.1% non-corrected radiochemical yield, good radiochemical purity (>95%) and high specific activity (>2000 Ci mmol-1). [11C]1 exhibited specific binding to D3 receptors using ex vivo autoradiography experiments with rat brain, but only 14-fold selectivity over D2 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 D3 receptors.