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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 6/2017

01-06-2017 | Original Article

PET imaging of α7 nicotinic acetylcholine receptors: a comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans

Authors: Ansel T. Hillmer, Songye Li, Ming-Qiang Zheng, Matthias Scheunemann, Shu-fei Lin, Nabeel Nabulsi, Daniel Holden, Richard Pracitto, David Labaree, Jim Ropchan, Rodrigo Teodoro, Winnie Deuther-Conrad, Irina Esterlis, Kelly P. Cosgrove, Peter Brust, Richard E. Carson, Yiyun Huang

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2017

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Abstract

Purpose

The α7 nicotinic acetylcholine receptor (nAChR) is implicated in many neuropsychiatric disorders, making it an important target for positron emission tomography (PET) imaging. The first aim of this work was to compare two α7 nAChRs PET radioligands, [18F]ASEM (3-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-6-([18F]fluorodibenzo[b,d]thiophene 5,5-dioxide) and [18F]DBT-10 (7-(1,4-diazabicyclo[3.2.2]nonan-4-yl)-2-([18F]fluorodibenzo[b,d]thiophene 5,5-dioxide), in nonhuman primates. The second aim was to assess further the quantification and test-retest variability of [18F]ASEM in humans.

Methods

PET scans with high specific activity [18F]ASEM or [18F]DBT-10 were acquired in three rhesus monkeys (one male, two female), and the kinetic properties of these radiotracers were compared. Additional [18F]ASEM PET scans with blocking doses of nicotine, varenicline, and cold ASEM were acquired separately in two animals. Next, six human subjects (five male, one female) were imaged with [18F]ASEM PET for 180 min, and arterial sampling was used to measure the parent input function. Different modeling approaches were compared to identify the optimal analysis method and scan duration for quantification of [18F]ASEM distribution volume (V T). In addition, retest scans were acquired in four subjects (three male, one female), and the test-retest variability of V T was assessed.

Results

In the rhesus monkey brain [18F]ASEM and [18F]DBT-10 exhibited highly similar kinetic profiles. Dose-dependent blockade of [18F]ASEM binding was observed, while administration of either nicotine or varenicline did not change [18F]ASEM V T. [18F]ASEM was selected for further validation because it has been used in humans. Accurate quantification of [18F]ASEM V T in humans was achieved using multilinear analysis with at least 90 min of data acquisition, resulting in V T values ranging from 19.6 ± 2.5 mL/cm3 in cerebellum to 25.9 ± 2.9 mL/cm3 in thalamus. Test-retest variability of V T was 11.7 ± 9.8%.

Conclusions

These results confirm [18F]ASEM as a suitable radiotracer for the imaging and quantification of α7 nAChRs in humans.
Appendix
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Metadata
Title
PET imaging of α7 nicotinic acetylcholine receptors: a comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans
Authors
Ansel T. Hillmer
Songye Li
Ming-Qiang Zheng
Matthias Scheunemann
Shu-fei Lin
Nabeel Nabulsi
Daniel Holden
Richard Pracitto
David Labaree
Jim Ropchan
Rodrigo Teodoro
Winnie Deuther-Conrad
Irina Esterlis
Kelly P. Cosgrove
Peter Brust
Richard E. Carson
Yiyun Huang
Publication date
01-06-2017
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2017
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-017-3621-8

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