Premium
Radiosynthesis and in vivo evaluation of [ 11 C]Ro‐647312: a novel NR1/2B subtype selective NMDA receptor radioligand
Author(s) -
Dollé Frédéric,
Valette Héric,
Demphel Stéphane,
Coulon Christine,
Ottaviani Michelle,
Bottlaender Michel,
Kassiou Michael
Publication year - 2004
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.877
Subject(s) - radiosynthesis , chemistry , nmda receptor , radioligand , ligand (biochemistry) , in vivo , desmethyl , high performance liquid chromatography , specific activity , solvent , radiochemistry , acetone , nuclear chemistry , receptor , stereochemistry , chromatography , organic chemistry , biochemistry , microbiology and biotechnology , metabolite , biology , enzyme
[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 [ 11 C]methyl triflate from the nor‐ methyl compound 2 . The reaction was performed in acetone as solvent using aqueous NaOH as base. Following HPLC purification [ 11 C]Ro‐647312 ([ 11 C]‐ 1 ) was obtained in 6.9–9.2% ( n = 3) radiochemical yield decay‐corrected based on starting [ 11 C]CO 2 , 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 [ 11 C]‐ 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. [ 11 C]‐ 1 does not possess the required properties for imaging NMDA receptors using positron emission tomography. Copyright © 2004 John Wiley & Sons, Ltd.