Neelamegam, RameshHellenbrand, TimSchroeder, Frederick AWang, ChangningHooker, Jacob2017-07-242014Neelamegam, Ramesh, Tim Hellenbrand, Frederick A. Schroeder, Changning Wang, and Jacob M. Hooker. 2014. “Imaging Evaluation of 5HT2CAgonists, [11C]WAY-163909 and [11C]Vabicaserin, Formed by Pictet–Spengler Cyclization.” Journal of Medicinal Chemistry 57 (4) (February 27): 1488–1494. doi:10.1021/jm401802f.0022-2623http://nrs.harvard.edu/urn-3:HUL.InstRepos:33490458The serotonin subtype 2C (5HT\(_{2C}\)) receptor is an emerging and promising drug target to treat several disorders of the human central nervous system. In this current report, two potent and selective 5HT\(_{2C}\) full agonists, WAY-163909 (2) and vabicaserin (3), were radiolabeled with carbon-11 via Pictet–Spengler cyclization with [\(^{11}\)C]formaldehyde and used in positron emission tomography (PET) imaging. Reaction conditions were optimized to exclude the major source of isotope dilution caused by the previously unknown breakdown of N,N-dimethylformamide (DMF) to formaldehyde at high temperature under mildly acid conditions. In vivo PET imaging was utilized to evaluate the pharmacokinetics and distribution of the carbon-11 labeled 5HT\(_{2C}\) agonists. Both radiolabeled molecules exhibit high blood–brain barrier (BBB) penetration and nonspecific binding, which was unaltered by preadministration of the unlabeled agonist. Our work demonstrates that Pictet–Spengler cyclization can be used to label drugs with carbon-11 to study their pharmacokinetics and for evaluation as PET radiotracers.en-USJournal Article10.1021/jm401802f