Evaluation of Two Potent and Selective PET Radioligands to Image COX-1 and COX-2 in Rhesus Monkeys

• Published in: Journal of Nuclear Medicine Vol. 59; no. 12; pp. 1907 - 1912
• Main Authors: Kim, Min-Jeong, Shrestha, Stal S., Cortes, Michelle, Singh, Prachi, Morse, Cheryl, Liow, Jeih-San, Gladding, Robert L., Brouwer, Chad, Henry, Katharine, Gallagher, Evan, Tye, George L., Zoghbi, Sami S., Fujita, Masahiro, Pike, Victor W., Innis, Robert B.
• Format: Journal Article
• Language: English
• Published: United States Society of Nuclear Medicine 01.12.2018
• Subjects: Animals; Brain; Carbon Radioisotopes; COX-2 inhibitors; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Cyclooxygenase-1; Cyclooxygenase-2; Female; Gastrointestinal system; Gastrointestinal tract; Infection/Inflammation; Inflammation; Intravenous administration; Kidneys; Macaca mulatta; Male; Monkeys; Organs; Ovaries; Positron emission; Positron emission tomography; Positron-Emission Tomography - methods; Positron-Emission Tomography - veterinary; Pyrimidines - administration & dosage; Pyrimidines - chemistry; Pyrimidines - metabolism; Radioisotopes; Radioligand Assay; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - pharmacokinetics; Spleen; Tissue Distribution; Tomography; Triazoles - chemistry; Triazoles - pharmacokinetics; Whole Body Imaging - methods; Whole Body Imaging - veterinary; cyclooxygenase-1; positron-emission tomography; nonsteroidal antiinflammatory agents; inflammation; cyclooxygenase-2
• ISSN: 0161-5505; 1535-5667; 2159-662X; 1535-5667
• DOI: 10.2967/jnumed.118.211144

This study assessed whether the newly developed PET radioligands C-PS13 and C-MC1 could image constitutive levels of cyclooxygenase (COX)-1 and COX-2, respectively, in rhesus monkeys. After intravenous injection of either radioligand, 24 whole-body PET scans were performed. To measure enzyme-specific uptake, scans of the 2 radioligands were also performed after administration of a nonradioactive drug preferential for either COX-1 or COX-2. Concurrent venous samples were obtained to measure parent radioligand concentrations. SUVs were calculated from 10 to 90 min. C-PS13 showed specific uptake in most organs, including spleen, gastrointestinal tract, kidneys, and brain, which was blocked by COX-1, but not COX-2, preferential inhibitors. Specific uptake of C-MC1 was not observed in any organ except the ovaries and possibly kidneys. The findings suggest that C-PS13 has adequate signal in monkeys to justify its extension to human subjects. In contrast, C-MC1 is unlikely to show significant signal in healthy humans, though it may be able to do so in inflammatory conditions.