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. [ 18 F]GE179 is a promising PET probe for imaging functional NMDA receptor alterations (activated or ‘open’ channel) with a high binding affinity (K d  = 2.4 nM). Here, we report the production of the NMDA receptor radioligand [ 18 F]GE179 in a current Good Manufacturing Practice (cGMP) facility through a one-pot two-step strategy. [ 18 F]GE179 was produced in approximately 110 min with a radiochemical yield of 12 ± 6% (n = 4, decay corrected), radiochemical purity >95%, molar activity of 146 ± 32 GBq/ μ mol (at the end of synthesis), an average mass of GE179 at 2.2  μ g/batch, and total impurities less than 0.5 μg/batch (n = 4). 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.