TY - JOUR T1 - Initial Evaluation of <sup>18</sup>F-GE-179, a Putative PET Tracer for Activated <em>N</em>-Methyl <span class="sc">d</span>-Aspartate Receptors JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 423 LP - 430 DO - 10.2967/jnumed.113.130641 VL - 55 IS - 3 AU - Colm J. McGinnity AU - Alexander Hammers AU - Daniela A. Riaño Barros AU - Sajinder K. Luthra AU - Paul A. Jones AU - William Trigg AU - Caroline Micallef AU - Mark R. Symms AU - David J. Brooks AU - Matthias J. Koepp AU - John S. Duncan Y1 - 2014/03/01 UR - http://jnm.snmjournals.org/content/55/3/423.abstract N2 - 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–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’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. ER -