RT Journal Article
SR Electronic
T1 First-in-Humans Brain PET Imaging of the GluN2B-Containing <em>N</em>-methyl-<span class="sc">d</span>-aspartate Receptor with (<em>R</em>)-<sup>11</sup>C-Me-NB1
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 936
OP 941
DO 10.2967/jnumed.121.262427
VO 63
IS 6
A1 Lucas Rischka
A1 Chrysoula Vraka
A1 Verena Pichler
A1 Sazan Rasul
A1 Lukas Nics
A1 Gregor Gryglewski
A1 Patricia Handschuh
A1 Matej Murgaš
A1 Godber M. Godbersen
A1 Leo R. Silberbauer
A1 Jakob Unterholzner
A1 Christoph Wotawa
A1 Ahmed Haider
A1 Hazem Ahmed
A1 Roger Schibli
A1 Thomas Mindt
A1 Markus Mitterhauser
A1 Wolfgang Wadsak
A1 Andreas Hahn
A1 Rupert Lanzenberger
A1 Marcus Hacker
A1 Simon M. Ametamey
YR 2022
UL http://jnm.snmjournals.org/content/63/6/936.abstract
AB The N-methyl-d-aspartate receptor (NMDAR) plays a crucial role in neurodegenerative diseases such as Alzheimer disease and in the treatment of major depression by fast-acting antidepressants such as ketamine. Given their broad implications, GluN2B-containing NMDARs have been of interest as diagnostic and therapeutic targets. Recently, (R)-11C-Me-NB1 was investigated preclinically and shown to be a promising radioligand for imaging GluN2B subunits. Here, we report on the performance characteristics of this radioligand in a first-in-humans PET study. Methods: Six healthy male subjects were scanned twice on a fully integrated PET/MR scanner with (R)-11C-Me-NB1 for 120 min. Brain uptake and tracer distribution over time were investigated by SUVs. Test–retest reliability was assessed with the absolute percentage difference and the coefficient of variation. Exploratory total volumes of distribution (VT) were computed using an arterial input function and the Logan plot as well as a constrained 2-tissue-compartment model with the ratio of rate constants between plasma and tissue compartments (K1/k2) coupled (2TCM). SUV was correlated with VT to investigate its potential as a surrogate marker of GluN2B expression. Results: High and heterogeneous radioligand uptake was observed across the entire gray matter with reversible kinetics within the scan time. SUV absolute percentage difference ranged from 6.9% to 8.5% and coefficient of variation from 4.9% to 6.0%, indicating a high test–retest reliability. A moderate correlation was found between SUV averaged from 70 to 90 min and VT using Logan plot (Spearman ρ = 0.44). Correlation between VT Logan and 2TCM was r = 0.76. Conclusion: The radioligand (R)-11C-Me-NB1 was highly effective in mapping GluN2B-enriched NMDARs in the human brain. With a heterogeneous uptake and a high test–retest reliability, this radioligand offers promise to deepen our understanding of the GluN2B-containing NMDAR in the pathophysiology and treatment of neuropsychiatric disease such as Alzheimer disease and major depression. Additionally, it could help in the selection of appropriate doses of GluN2B-targeting drugs.