Jennifer M Coughlin1,2, Stephanie Slania3, Yong Du2, Hailey B Rosenthal2, Wojciech G Lesniak2, Il Minn2, Gwenn S Smith1,2, Robert F Dannals2, Hiroto Kuwabara2, Dean F Wong1,2,4,5, Yuchuan Wang2, Andrew G Horti2, Martin G Pomper6,2,3. 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 (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 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.
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 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 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.
Authors: Robert B Innis; Vincent J Cunningham; Jacques Delforge; Masahiro Fujita; Albert Gjedde; Roger N Gunn; James Holden; Sylvain Houle; Sung-Cheng Huang; Masanori Ichise; Hidehiro Iida; Hiroshi Ito; Yuichi Kimura; Robert A Koeppe; Gitte M Knudsen; Juhani Knuuti; Adriaan A Lammertsma; Marc Laruelle; Jean Logan; Ralph Paul Maguire; Mark A Mintun; Evan D Morris; Ramin Parsey; Julie C Price; Mark Slifstein; Vesna Sossi; Tetsuya Suhara; John R Votaw; Dean F Wong; Richard E Carson Journal: J Cereb Blood Flow Metab Date: 2007-05-09 Impact factor: 6.200
Authors: Osama Sabri; Georg-Alexander Becker; Philipp M Meyer; Swen Hesse; Stephan Wilke; Susanne Graef; Marianne Patt; Julia Luthardt; Gudrun Wagenknecht; Alexander Hoepping; René Smits; Annegret Franke; Bernhard Sattler; Bernd Habermann; Petra Neuhaus; Steffen Fischer; Solveig Tiepolt; Winnie Deuther-Conrad; Henryk Barthel; Peter Schönknecht; Peter Brust Journal: Neuroimage Date: 2015-05-30 Impact factor: 6.556
Authors: J Logan; J S Fowler; N D Volkow; A P Wolf; S L Dewey; D J Schlyer; R R MacGregor; R Hitzemann; B Bendriem; S J Gatley Journal: J Cereb Blood Flow Metab Date: 1990-09 Impact factor: 6.200
Authors: A Wevers; L Burghaus; N Moser; B Witter; O K Steinlein; U Schütz; B Achnitz; U Krempel; S Nowacki; K Pilz; J Stoodt; J Lindstrom; R A De Vos; E N Jansen Steur; H Schröder Journal: Behav Brain Res Date: 2000-08 Impact factor: 3.332
Authors: Andrew G Horti; Hiroto Kuwabara; Daniel P Holt; Robert F Dannals; Dean F Wong Journal: J Labelled Comp Radiopharm Date: 2013 Mar-Apr Impact factor: 1.921
Authors: Hiroto Kuwabara; Yongjun Gao; Michael Stabin; Jennifer Coughlin; Sridhar Nimmagadda; Robert F Dannals; Martin G Pomper; Andrew G Horti Journal: Mol Imaging Biol Date: 2017-04 Impact factor: 3.488
Authors: Shivesh Ghura; Robert Gross; Kelly Jordan-Sciutto; Jacob Dubroff; Robert Schnoll; Ronald G Collman; Rebecca L Ashare Journal: J Neuroimmune Pharmacol Date: 2019-12-13 Impact factor: 4.147