期刊
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
卷 47, 期 13, 页码 3143-3151出版社
SPRINGER
DOI: 10.1007/s00259-020-04855-2
关键词
Cyclooxygenase-1; Positron emission tomography; Inflammation; Test-retest reliability; Neuroimaging
资金
- Intramural Research Program of the National Institute of Mental Health, National Institutes of Health [ZIAMH002795, ZIAMH002793]
- NATIONAL INSTITUTE OF MENTAL HEALTH [ZIAMH002793] Funding Source: NIH RePORTER
Purpose This study assessed whether the newly developed PET radioligand [C-11]PS13, which has shown excellent in vivo selectivity in previous animal studies, could be used to quantify constitutive levels of cyclooxygenase-1 (COX-1) in healthy human brain. Methods Brain test-retest scans with concurrent arterial blood samples were obtained in 10 healthy individuals. The one- and unconstrained two-tissue compartment models, as well as the Logan graphical analysis were compared, and test-retest reliability and time-stability of total distribution volume (V-T) were assessed. Correlation analyses were conducted between brain regional V-T and COX-1 transcript levels provided in the Allen Human Brain Atlas. Results In the brain, [C-11]PS13 showed highest uptake in the hippocampus and occipital cortex. The pericentral cortex also showed relatively higher uptake compared with adjacent neocortices. The two-tissue compartment model showed the best fit in all the brain regions, and the results from the Logan graphical analysis were consistent with those from the two-tissue compartment model. V-T values showed excellent test-retest variability (range 6.0-8.5%) and good reliability (intraclass correlation coefficient range 0.74-0.87). V-T values also showed excellent time-stability in all brain regions, confirming that there was no radiometabolite accumulation and that shorter scans were still able to reliably measure V-T. Significant correlation was observed between V-T and COX-1 transcript levels (r = 0.82, P = 0.007), indicating that [C-11]PS13 binding reflects actual COX-1 density in the human brain. Conclusions These results from the first-in-human evaluation of the ability of [C-11]PS13 to image COX-1 in the brain justifies extending the study to disease populations with neuroinflammation.
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