Synthesis and pre-clinical evaluation of a potential radiotracer for PET imaging of the dopamine D3 receptor. Issue 8 (5th July 2018)

• Record Type: Journal Article
• Authors: Stewart, Megan N.; Shao, Xia; Desmond, Timothy J.; Forrest, Taylor J.; Arteaga, Janna; Stauff, Jenelle; Scott, Peter J. H.
• Is Part Of: MedChemComm. Volume 9:Issue 8(2018)
• Page Start: 1315
• Page End: 1322
• Publication Date: 2018-07-05
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c8md00094h
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : There is considerable interest in using PET imaging to quantify dopamine D3 receptors. We report a new D3 -selective radioligand, and describe preclincial evaluation in rodent using ex vivo autoradiography and in vivo PET imaging. Abstract : 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 ([ 11 C]1 ), and its initial preclincial evaluation as a potential PET radiotracer for in vivo imaging of D3 receptors.[ 11 C]1 was prepared via [ 11 C]CO2 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 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.