Automated production of a N-methyl-D-aspartate receptor radioligand [18F]GE179 for clinical use.

Abstract

N-Methyl-d-aspartate (NMDA) receptors are ligand and voltage-gated heteromeric ion channel receptors. Excessive activation of NMDA receptors is implicated in many neurological and psychiatric disorders, including ischemic stroke, neuropathic pain, epilepsy, drug addition, Alzheimer s disease, and schizophrenia. [18F]GE179 is a promising PET probe for imaging functional NMDA receptor alterations (activated or open channel) with a high binding affinity (Kd\u202f=\u202f2.4\u202fnM). Here, we report the production of the NMDA receptor radioligand [18F]GE179 in a current Good Manufacturing Practice (cGMP) facility through a one-pot two-step strategy. [18F]GE179 was produced in approximately 110\u202fmin with a radiochemical yield of 12\u202f±\u202f6% (n\u202f=\u202f4, decay corrected), radiochemical purity >95%, molar activity of 146\u202f±\u202f32 GBq/μmol (at the end of synthesis), an average mass of GE179 at 2.2\u202fμg/batch, and total impurities less than 0.5\u202fμg/batch (n\u202f=\u202f4). The radiopharmaceutical dose meets all quality control (QC) criteria for human use, and is suitable for clinical PET studies of activated NMDA receptor ion channels.