F-18-Xtra Pet For Enhanced Imaging Of The Extrathalamic Alpha 4 Beta 2 Nicotinic Acetylcholine Receptor
JOURNAL OF NUCLEAR MEDICINE(2018)
Abstract
Reduced density of the alpha 4 beta 2 nicotinic acetylcholine receptor (alpha 4 beta 2-nAChR) in the cortex and hippocampus of the human brain has been reported in aging and patients with neurodegenerative disease. This study assessed the pharmacokinetic behavior of F-18-(-)-JHU86428 (F-18-XTRA), a new radiotracer for in vivo PET imaging of the alpha 4 beta 2-nAChR, particularly in extrathalamic regions of interest in which the alpha 4 beta 2-nAChR is less densely expressed than in thalamus. F-18-XTRA was also used to evaluate the alpha 4 beta 2-nAChR in the hippocampus in human aging. Methods: Seventeen healthy nonsmoker adults (11 men, 6 women; age, 30-82 y) underwent PET neuroimaging over 90 or 180 min in a high-resolution research tomograph after bolus injection of F-18-XTRA. Methods to quantify binding of F-18-XTRA to the alpha 4 beta 2-nAChR in the human brain were compared, and the relationship between age and binding in the hippocampus was tested. Results: F-18-XTRA rapidly entered the brain, and time-activity curves peaked within 10 min after injection for extrathalamic regions and at approximately 70 min in the thalamus. The 2-tissue-compartment model (2TCM) predicted the regional time-activity curves better than the 1-tissue-compartment model, and total distribution volume (V-T) was well identified by the 2TCM in all ROIs. V-T values estimated using Logan analysis with metabolitecorrected arterial input were highly correlated with those from the 2TCM in all regions, and values from 90-min scan duration were on average within 5% of those values from 180 min of data. Parametric images of V-T were consistent with the known distribution of the alpha 4 beta 2-nAChR across the brain. Finally, an inverse correlation between V-T in the hippocampus and age was observed. Conclusion: Our results extend support for use of F-18-XTRA with 90 min of emission scanning in quantitative human neuroimaging of the extrathalamic alpha 4 beta 2-nAChR, including in studies of aging.
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Key words
F-18-XTRA, PET imaging, nicotinic acetylcholine receptor, healthy aging
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