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

• Published in: European journal of nuclear medicine and molecular imaging Vol. 47; no. 13; pp. 3143 - 3151
• Main Authors: Kim, Min-Jeong, Lee, Jae-Hoon, Juarez Anaya, Fernanda, Hong, Jinsoo, Miller, William, Telu, Sanjay, Singh, Prachi, Cortes, Michelle Y., Henry, Katharine, Tye, George L., Frankland, Michael P., Montero Santamaria, Jose A., Liow, Jeih-San, Zoghbi, Sami S., Fujita, Masahiro, Pike, Victor W., Innis, Robert B.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2020; Springer Nature B.V
• Subjects: Animals; Brain; Brain - diagnostic imaging; Brain - metabolism; Cardiology; Correlation analysis; Correlation coefficients; Cyclooxygenase 1 - metabolism; Cyclooxygenase-1; Evaluation; Human performance; Humans; Imaging; In vivo methods and tests; Inflammation; Medicine; Medicine & Public Health; Neuroimaging; Neurology; Nuclear Medicine; Occipital lobe; Oncology; Original Article; Orthopedics; Population studies; Positron emission tomography; Radiology; Radiopharmaceuticals; Reliability analysis; Reproducibility of Results; Selectivity; Stability analysis; Transcription; Neuroimaging; Inflammation; Cyclooxygenase-1; Test-retest reliability; Positron emission tomography
• ISSN: 1619-7070; 1619-7089
• DOI: 10.1007/s00259-020-04855-2

Purpose This study assessed whether the newly developed PET radioligand [ 11 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 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, [ 11 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 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 [ 11 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 [ 11 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.