Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2014
Initial evaluation of 18F-GE-179, a putative PET Tracer for activated N-methyl D-aspartate receptors.
Клиническое исследованиеСтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
McGinnity Colm J, Hammers Alexander, Riaño Barros Daniela A, Luthra Sajinder K, Jones Paul A, Trigg William, Micallef Caroline, Symms Mark R, Brooks David J, Koepp Matthias J, Duncan John S
Аннотация
UNLABELLED: 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. (18)F-GE-179 is a novel radioligand that selectively binds to the open/active state of the NMDA receptor ion channel, displacing the binding of (3)H-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 (18)F-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 (V(T)) 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 (18)F-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 V(T) (Spearman ρ = 0.398; P = 0.003). Between-subject coefficients of variation of V(T) ranged between 12% and 16%. Voxelwise RS-ESA yielded similar V(T)s and coefficients of variation.
CONCLUSION: (18)F-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 (18)F-GE-179 VT is feasible both within regions of interest and at the voxel level. The specificity of (18)F-GE-179 binding, however, requires further characterization with in vivo studies using activation and disease models.
METHODS: Nine healthy participants (6 men, 3 women; median age, 37 y) each underwent a 90-min PET scan after an intravenous injection of (18)F-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 (V(T)) 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 (18)F-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 V(T) (Spearman ρ = 0.398; P = 0.003). Between-subject coefficients of variation of V(T) ranged between 12% and 16%. Voxelwise RS-ESA yielded similar V(T)s and coefficients of variation.
CONCLUSION: (18)F-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 (18)F-GE-179 VT is feasible both within regions of interest and at the voxel level. The specificity of (18)F-GE-179 binding, however, requires further characterization with in vivo studies using activation and disease models.