Radiosynthesis and in vivo evaluation of [11C]Ro‐647312: a novel NR1/2B subtype selective NMDA receptor radioligand

2‐(3,4‐Dihydro‐1H‐isoquinolin‐2‐yl)‐pyridin‐4‐yl]‐dimethylamine, Ro‐647312 ( 1 ) represents a new novel class of NR1/2B subtype selective NMDA ligand. Ro‐647312 has been radiolabelled with carbon‐11 using ¹¹C]methyl triflate from the nor‐methyl compound 2 . The reaction was performed in acetone as solvent using aqueous NaOH as base. Following HPLC purification ¹¹C]Ro‐647312 (¹¹C]‐ 1 ) was obtained in 6.9–9.2% (n = 3) radiochemical yield decay‐corrected based on starting ¹¹C]CO₂, with specific radioactivity measured at the end of the radiosynthesis ranging from 1.0 to 3.5 Ci/µmol (37–129 GBq/µmol). Radiochemical and chemical purities were assessed as >99 and >95%, respectively. Following i.v. injection of ¹¹C]‐ 1 in rat, the distribution of radioactivity was homogeneous in all brain structures and did not correlate with the known distribution of NR2B subunits. The radioactivity observed in plasma was also higher than any brain structure throughout the time course of the experiment. ¹¹C]‐ 1 does not possess the required properties for imaging NMDA receptors using positron emission tomography. Copyright © 2004 John Wiley & Sons, Ltd.