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

Purpose: This study assessed whether the newly developed PET radioligand [C]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) were assessed. Correlation analyses were conducted between brain regional V and COX-1 transcript levels provided in the Allen Human Brain Atlas.

Results: In the brain, [C]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 values showed excellent test-retest variability (range 6.0-8.5%) and good reliability (intraclass correlation coefficient range 0.74-0.87). V 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. Significant correlation was observed between V and COX-1 transcript levels (r = 0.82, P = 0.007), indicating that [C]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]PS13 to image COX-1 in the brain justifies extending the study to disease populations with neuroinflammation.

Clinical Trial Registration: NCT03324646 at https://clinicaltrials.gov/ . Registered October 30, 2017. Retrospectively registered.