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First-in-human evaluation of [C-11]PS13, a novel PET radioligand, to quantify cyclooxygenase-1 in the brain

Authors
 Kim, Min-Jeong  ;  Lee, Jae-Hoon  ;  Anaya, Fernanda Juarez  ;  Hong, Jinsoo  ;  Miller, William  ;  Telu, Sanjay  ;  Singh, Prachi  ;  Cortes, Michelle Y.  ;  Henry, Katharine  ;  Tye, George L.  ;  Frankland, Michael P.  ;  Santamaria, Jose A. Montero  ;  Liow, Jeih-San  ;  Zoghbi, Sami S.  ;  Fujita, Masahiro  ;  Pike, Victor W.  ;  Innis, Robert B. 
Citation
 EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, Vol.47(13) : 3143-3151, 2020-12 
Journal Title
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
ISSN
 1619-7070 
Issue Date
2020-12
Keywords
Cyclooxygenase-1 ; Positron emission tomography ; Inflammation ; Test-retest reliability ; Neuroimaging
Abstract
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.
Full Text
https://link.springer.com/article/10.1007/s00259-020-04855-2
DOI
10.1007/s00259-020-04855-2
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Lee, Jae Hoon(이재훈) ORCID logo https://orcid.org/0000-0002-9898-9886
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/181794
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