Synthesis and characterization of N ‐(2‐chloro‐5‐methylthiophenyl)‐ N ′‐(3‐methylthiophenyl)‐ N ′‐[ 11 C]methylguanidine [ 11 C]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 [ 11 C]CNS 5161 by means of [ 11 C]methylation of the desmethyl guanidine precursor. [ 11 C]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 © 2005 John Wiley & Sons, Ltd.