18F-XTRA PET for Enhanced Imaging of the Extrathalamic ?4?2 Nicotinic Acetylcholine Receptor.

ABSTRACT: Reduced density of the ?4?2 nicotinic acetylcholine receptor (?4?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 18F-(-)-JHU86428 (18F-XTRA), a new radiotracer for in vivo PET imaging of the ?4?2-nAChR, particularly in extrathalamic regions of interest in which the ?4?2-nAChR is less densely expressed than in thalamus. 18F-XTRA was also used to evaluate the ?4?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 18F-XTRA. Methods to quantify binding of 18F-XTRA to the ?4?2-nAChR in the human brain were compared, and the relationship between age and binding in the hippocampus was tested. Results: 18F-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 (VT) was well identified by the 2TCM in all ROIs. VT values estimated using Logan analysis with metabolite-corrected 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 VT were consistent with the known distribution of the ?4?2-nAChR across the brain. Finally, an inverse correlation between VT in the hippocampus and age was observed. Conclusion: Our results extend support for use of 18F-XTRA with 90 min of emission scanning in quantitative human neuroimaging of the extrathalamic ?4?2-nAChR, including in studies of aging.

SUBMITTER: Coughlin JM 

PROVIDER: S-EPMC6167533 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature