Synthesis and characterization of N-(2-chloro-5-methylthiophenyl)-N′-(3-methylthiophenyl)-N′- [11C]methylguanidine [11C]CNS 5161, a candidate PET tracer for functional imaging of NMDA receptors

N-methyl-D-aspartate (NMDA) receptors play a key role in excitatory neurotransmission and are linked to a variety of acute and chronic neurodegenerative diseases including epilepsy, schizophrenia, Parkinson's disease and drug abuse. N-(2-chloro-5-methylthiophenyl)-N'-(3-methylthiophenyl)-N'-methylguanidine (CNS 5161) is a high affinity ligand (Ki = 1.87 +/- 0.25 nM) for the NMDA PCP site, which potentially can be used for functional imaging of this receptor. Herein we report the synthesis of the corresponding positron emission tomography (PET) tracer [C-11]CNS 5161 by means of [C-11]methylation of the desmethyl guanidine precursor. [C-11]CNS 5161 was synthesized with a decay corrected radiochemical yield of 10% within 45 min after end of bombardment (EOB). The final product was prepared in a sterile saline solution suitable for clinical studies with a radiochemical purity of > 96% and a specific activity of 41 GBq/mmol at time of injection. Copyright (c) 2005 John Wiley & Sons, Ltd.