PET Quantification of [18F]VAT in Human Brain and Its Test-Retest Reproducibility and Age Dependence

John L O'Donnell; Anil Kumar Soda; Hao Jiang; Scott A Norris; Baijayanta Maiti; Morvarid Karimi; Meghan C Campbell; Stephen M Moerlein; Zhude Tu; Joel S Perlmutter

doi:10.2967/jnumed.123.266860

PET Quantification of [¹⁸F]VAT in Human Brain and Its Test-Retest Reproducibility and Age Dependence

J Nucl Med. 2024 Apr 11:jnumed.123.266860. doi: 10.2967/jnumed.123.266860. Online ahead of print.

Authors

John L O'Donnell¹, Anil Kumar Soda², Hao Jiang², Scott A Norris^{3

2}, Baijayanta Maiti^{3

2}, Morvarid Karimi^{3

2}, Meghan C Campbell^{3

2}, Stephen M Moerlein^{2

4}, Zhude Tu², Joel S Perlmutter^{3

2

5}

Affiliations

¹ Neurology, Washington University in Saint Louis, St. Louis, Missouri; jodonn@wustl.edu.
² Radiology, Washington University in Saint Louis, St. Louis, Missouri.
³ Neurology, Washington University in Saint Louis, St. Louis, Missouri.
⁴ Biochemistry and Molecular Biophysics, Washington University in Saint Louis, St. Louis, Missouri; and.
⁵ Neuroscience, Physical, and Occupational Therapy, Washington University in Saint Louis, St. Louis, Missouri.

PMID: 38604762
DOI: 10.2967/jnumed.123.266860

Abstract

Molecular imaging of brain vesicular acetylcholine transporter provides a biomarker to explore cholinergic systems in humans. We aimed to characterize the distribution of, and optimize methods to quantify, the vesicular acetylcholine transporter-specific tracer (-)-(1-(8-(2-[¹⁸F]fluoroethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)-piperidin-4-yl)(4-fluorophenyl)methanone ([¹⁸F]VAT) in the brain using PET. Methods: Fifty-two healthy participants aged 21-97 y had brain PET with [¹⁸F]VAT. [³H]VAT autoradiography identified brain areas devoid of specific binding in cortical white matter. PET image-based white matter reference region size, model start time, and duration were optimized for calculations of Logan nondisplaceable binding potential (BP_ND). Ten participants had 2 scans to determine test-retest variability. Finally, we analyzed age-dependent differences in participants. Results: [¹⁸F]VAT was widely distributed in the brain, with high striatal, thalamic, amygdala, hippocampal, cerebellar vermis, and regionally specific uptake in the cerebral cortex. [³H]VAT autoradiography-specific binding and PET [¹⁸F]VAT uptake were low in white matter. [¹⁸F]VAT SUVs in the white matter reference region correlated with age, requiring stringent erosion parameters. Logan BP_ND estimates stabilized using at least 40 min of data starting 25 min after injection. Test-retest variability had excellent reproducibility and reliability in repeat BP_ND calculations for 10 participants (putamen, 6.8%; r > 0.93). We observed age-dependent decreases in the caudate and putamen (multiple comparisons corrected) and in numerous cortical regions. Finally, we provide power tables to indicate potential mean differences that can be detected between 2 groups of participants. Conclusion: These results validate a reference region for BP_ND calculations and demonstrate the viability, reproducibility, and utility of using the [¹⁸F]VAT tracer in humans to quantify cholinergic pathways.

Keywords: PET; acetylcholine; brain; cholinergic; human.

Abstract

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