RT Journal Article
SR Electronic
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
FD Society of Nuclear Medicine
SP 423
OP 430
DO 10.2967/jnumed.113.130641
VO 55
IS 3
A1 Colm J. McGinnity
A1 Alexander Hammers
A1 Daniela A. Riaño Barros
A1 Sajinder K. Luthra
A1 Paul A. Jones
A1 William Trigg
A1 Caroline Micallef
A1 Mark R. Symms
A1 David J. Brooks
A1 Matthias J. Koepp
A1 John S. Duncan
YR 2014
UL http://jnm.snmjournals.org/content/55/3/423.abstract
AB 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.