@article {McGinnity423, author = {Colm J. McGinnity and Alexander Hammers and Daniela A. Ria{\~n}o Barros and Sajinder K. Luthra and Paul A. Jones and William Trigg and Caroline Micallef and Mark R. Symms and David J. Brooks and Matthias J. Koepp and John S. Duncan}, title = {Initial Evaluation of 18F-GE-179, a Putative PET Tracer for Activated N-Methyl d-Aspartate Receptors}, volume = {55}, number = {3}, pages = {423--430}, year = {2014}, doi = {10.2967/jnumed.113.130641}, publisher = {Society of Nuclear Medicine}, abstract = {N-methyl d-aspartate (NMDA) ion channels play a key role in a wide range of physiologic (e.g., memory and learning tasks) and pathologic processes (e.g., excitotoxicity). To date, suitable PET markers of NMDA ion channel activity have not been available. 18F-GE-179 is a novel radioligand that selectively binds to the open/active state of the NMDA receptor ion channel, displacing the binding of 3H-tenocyclidine from the intrachannel binding site with an affinity of 2.4 nM. No significant binding was observed with 10 nM GE-179 at 60 other neuroreceptors, channels, or transporters. We describe the kinetic behavior of the radioligand in vivo in humans. Methods: Nine healthy participants (6 men, 3 women; median age, 37 y) each underwent a 90-min PET scan after an intravenous injection of 18F-GE-179. Continuous arterial blood sampling over the first 15 min was followed by discrete blood sampling over the duration of the scan. Brain radioactivity (KBq/mL) was measured in summation images created from the attenuation- and motion-corrected dynamic images. Metabolite-corrected parent plasma input functions were generated. We assessed the abilities of 1-, 2-, and 3-compartment models to kinetically describe cerebral time{\textendash}activity curves using 6 bilateral regions of interest. Parametric volume-of-distribution (VT) images were generated by voxelwise rank-shaping regularization of exponential spectral analysis (RS-ESA). Results: A 2-brain-compartment, 4-rate-constant model best described the radioligand{\textquoteright}s kinetics in normal gray matter of subjects at rest. At 30 min after injection, 37\% of plasma radioactivity represented unmetabolized 18F-GE-179. The highest mean levels of gray matter radioactivity were seen in the putamina and peaked at 7.5 min. A significant positive correlation was observed between K1 and VT (Spearman ρ = 0.398; P = 0.003). Between-subject coefficients of variation of VT ranged between 12\% and 16\%. Voxelwise RS-ESA yielded similar VTs and coefficients of variation. Conclusion: 18F-GE-179 exhibits high and rapid brain extraction, with a relatively homogeneous distribution in gray matter and acceptable between-subject variability. Despite its rapid peripheral metabolism, quantification of 18F-GE-179 VT is feasible both within regions of interest and at the voxel level. The specificity of 18F-GE-179 binding, however, requires further characterization with in vivo studies using activation and disease models.}, issn = {0161-5505}, URL = {https://jnm.snmjournals.org/content/55/3/423}, eprint = {https://jnm.snmjournals.org/content/55/3/423.full.pdf}, journal = {Journal of Nuclear Medicine} }