Selective Mapping of Brain COX-1 with [11C]PS13: Pharmacokinetic Evidence from human PET Imaging

Selective Mapping of Brain COX-1 with [11C]PS13: Pharmacokinetic Evidence from human PET Imaging

Background and aim: Arachidonic acid is converted by cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) to prostaglandin H2, which has proinflammatory properties. The new PET radioligand [11 C]PS13 exhibits superior in vivo selectivity for COX-1 in nonhuman primates compared to COX-2. This study...

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Main Authors: Kiana Orangi, Kimiya Batebi, Farnoosh Vosough, Mahdiyeh Nozad Varjovi, Fatemeh Salehian, Sahar Mesbah, Mehrnaz Salahi, Sajjad Hajihosseini, Mohammad Yousef Fazel, Saman Zaman, Reza Hossein Zadeh, Alaleh Alizadeh, Mahsa Asadi Anar, Niloofar Deravi
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:IBRO Neuroscience Reports
Subjects:
Cyclooxygenase-1 (COX-1)
PET imaging
Neuroinflammation
[11 C]PS13
NSAIDs
COX-selectivity
Online Access:http://www.sciencedirect.com/science/article/pii/S2667242125000594
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Summary:Background and aim: Arachidonic acid is converted by cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) to prostaglandin H2, which has proinflammatory properties. The new PET radioligand [11 C]PS13 exhibits superior in vivo selectivity for COX-1 in nonhuman primates compared to COX-2. This study aimed to investigate [11 C]PS13 pharmacologically selectivity and substantial binding to COX-1 in the human brain. Material and methods: Eight healthy volunteers had baseline [11 C]PS13 brain PET scans, and then images were blocked with either aspirin, celecoxib, or ketoprofen. The participants underwent two 90-minute [11 C]PS13 PET scans with radio metabolite-corrected arterial input function at baseline and approximately two hours after they received 75 mg of ketoprofen orally Result: This study on [11 C]PS13 brain PET scans showed that ketoprofen and celecoxib selectively bind to COX-1 in the human brain. The occupancy plot showed a positive correlation with plasma ketoprofen concentration, with the highest binding potentials in the calcarine and lingual gyrus of the occipital region. The occupancy for COX-1 was about 49 % and 27 % for ketoprofen and celecoxib, respectively. Conclusion: Ketoprofen demonstrated the highest selectivity for COX-1, while celecoxib exhibited partial occupancy likely due to dose- or time-dependent COX-1 inhibition. Aspirin showed minimal effect. Given the small sample size (n = 8), further studies with larger cohorts are warranted to confirm these findings and assess pharmacokinetic influences more thoroughly.
ISSN:2667-2421

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