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

Xuyi Yue; Yangchun Xin; Harry T Chugani; Diane C Chugani; Shaohui Zhang

doi:10.1016/j.apradiso.2019.03.035

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

Appl Radiat Isot. 2019 Jun:148:246-252. doi: 10.1016/j.apradiso.2019.03.035. Epub 2019 Mar 27.

Authors

Xuyi Yue¹, Yangchun Xin¹, Harry T Chugani², Diane C Chugani³, Shaohui Zhang⁴

Affiliations

¹ Department of Research, Katzin Diagnostic & Research PET/MRI Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA.
² Department of Neurology, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA.
³ Communication Sciences and Disorders, College of Health Sciences, University of Delaware, Newark, DE, 19713, USA.
⁴ Department of Research, Katzin Diagnostic & Research PET/MRI Center, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, 19803, USA. Electronic address: Shaohui.Zhang@nemours.org.

PMID: 31026789
DOI: 10.1016/j.apradiso.2019.03.035

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 (K_d = 2.4 nM). 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 min with a radiochemical yield of 12 ± 6% (n = 4, decay corrected), radiochemical purity >95%, molar activity of 146 ± 32 GBq/μmol (at the end of synthesis), an average mass of GE179 at 2.2 μg/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.

Keywords: Current good manufacturing practice; N-Methyl-d-aspartate receptors; Radiosynthesis; [(18)F]GE179.

MeSH terms

Automation
Fluorine Radioisotopes / metabolism*
Quality Control
Radioligand Assay
Radiopharmaceuticals / chemical synthesis*
Radiopharmaceuticals / metabolism
Radiopharmaceuticals / therapeutic use*
Receptors, N-Methyl-D-Aspartate / metabolism*

Substances

Fluorine Radioisotopes
Radiopharmaceuticals
Receptors, N-Methyl-D-Aspartate