Synthesis and in vivo evaluation of [ 11C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors

• Published in: Nuclear medicine and biology 2003-05, Vol.30 (4), p.435-439
• Main Authors: Dumont, Filip, Waterhouse, Rikki N., Montoya, Julie A., Mattner, Filomena, Katsifis, Andrew, Kegeles, Lawrence S., Laruelle, Marc
• Format: Article
• Language: English
• Subjects: [ 11C]Zolpidem; Agonist; Animals; Biological and medical sciences; Central benzodiazepine receptors; GABA Agonists - chemical synthesis; GABA Agonists - pharmacokinetics; GABA Agonists - pharmacology; Male; Medical sciences; Papio; PET; Pyridines - chemical synthesis; Pyridines - pharmacokinetics; Pyridines - pharmacology; Rats; Rats, Wistar; Receptors, GABA-A - drug effects; Tissue Distribution; Tomography, Emission-Computed
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/S0969-8051(03)00006-4

The synthesis and evaluation of [ 11C]zolpidem, an imidazopyridine with agonist properties at central benzodiazepine receptors, is reported herein. The reaction of desmethylzolpidem with [ 11C] methyl iodide afforded the title compound [ 11C]zolpidem in a yield of 19.19 ± 3.23% in 41 ± 2 min in specific activities of 0.995-1.19 Ci/μmol (1.115 ± 0.105 Ci/μmol) (n = 3; decay corrected, EOB). The amount of radioactivity in the brain after tail vein injection in male Wistar rats was low, and the regional distribution was homogeneous and not consistent with the known distribution of the central benzodiazepine receptors. The frontal cortex/cerebellum ratio was not significantly greater than one (1.007 ± 0.266 at 5 min) and did not increase from 5 to 40 min post-injection. A PET brain imaging study in one baboon confirmed the results obtained in rats. Therefore, it can be concluded that [ 11C]zolpidem is not a suitable tracer for in vivo visualization of central benzodiazepine receptors.