18F-XTRA PET for Enhanced Imaging of the Extrathalamic α4β2 Nicotinic Acetylcholine Receptor

Jennifer M Coughlin; Stephanie Slania; Yong Du; Hailey B Rosenthal; Wojciech G Lesniak; Il Minn; Gwenn S Smith; Robert F Dannals; Hiroto Kuwabara; Dean F Wong; Yuchuan Wang; Andrew G Horti; Martin G Pomper

doi:10.2967/jnumed.117.205492

¹⁸F-XTRA PET for Enhanced Imaging of the Extrathalamic α4β2 Nicotinic Acetylcholine Receptor

J Nucl Med. 2018 Oct;59(10):1603-1608. doi: 10.2967/jnumed.117.205492. Epub 2018 Mar 1.

Authors

Jennifer M Coughlin^{1

2}, Stephanie Slania³, Yong Du², Hailey B Rosenthal², Wojciech G Lesniak², Il Minn², Gwenn S Smith^{1

2}, Robert F Dannals², Hiroto Kuwabara², Dean F Wong^{1

2

4

5}, Yuchuan Wang², Andrew G Horti², Martin G Pomper^{6

2

3}

Affiliations

¹ Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland.
² Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions, Baltimore, Maryland.
³ Department of Biomedical Engineering, Johns Hopkins Medical Institutions, Baltimore, Maryland.
⁴ Department of Neuroscience, Johns Hopkins Medical Institutions, Baltimore, Maryland; and.
⁵ Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, Maryland.
⁶ Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland mpomper@jhmi.edu.

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 (V_T) was well identified by the 2TCM in all ROIs. V_T 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 V_T were consistent with the known distribution of the α4β2-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 ¹⁸F-XTRA with 90 min of emission scanning in quantitative human neuroimaging of the extrathalamic α4β2-nAChR, including in studies of aging.

Keywords: 18F-XTRA; PET imaging; healthy aging; nicotinic acetylcholine receptor.

Publication types

Clinical Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Aging / metabolism
Aging / physiology
Brain / diagnostic imaging*
Brain / metabolism*
Brain / physiology
Cognition
Female
Hippocampus / diagnostic imaging
Hippocampus / metabolism
Humans
Male
Middle Aged
Positron-Emission Tomography*
Receptors, Nicotinic / metabolism*

Substances

Receptors, Nicotinic
nicotinic receptor alpha4beta2

Abstract

Publication types

MeSH terms

Substances

Grants and funding