18F-XTRA PET for enhanced imaging of the extrathalamic α4β2 nicotinic acetylcholine receptor

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Abstract

Reduced density of the α4β2 nicotinic acetylcholine receptor (α4β2- 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 α4β2-nAChR, particularly in extrathalamic regions of interest in which the α4β2-nAChR is less densely expressed than in thalamus. 18F-XTRA was also used to evaluate the α4β2-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 α4β2-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 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 VT were consistent with the known distribution of the α4β2- 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 α4β2- nAChR, including in studies of aging.

Original languageEnglish (US)
Pages (from-to)1603-1608
Number of pages6
JournalJournal of Nuclear Medicine
Volume59
Issue number10
DOIs
StatePublished - Oct 1 2018

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Keywords

  • F-XTRA
  • Healthy aging
  • Nicotinic acetylcholine receptor
  • PET imaging

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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