The PET radioligand [11C]PS13 shows high specific binding in human brain of cyclooxygenase-1, a biomarker for microglia

Authors

• BL Stangl
• JW Luk
• RV Shah
• CL Vaughan
• AJ Waters
• ML Schwandt
• D Goldman
• N Diazgranandos
• VA Ramchandani

Abstract

Purpose/ Background: Neuroinflammation is associated with various neurodegenerative forms of dementia, including Alzheimer's disease. Such diseases may be associated with neuroinflammation. Cyclooxygenases (COX) produce inflammatory mediators Thus, PET radioligands for COX are potentially useful for the study of neuroinflammation.
We recently developed [11C]PS13, a highly selective radioligand for COX-1, a major isoform of COX.
Our objective was to accurately estimate the specific binding of [11C]PS13 to COX-1 in healthy human brain using scans performed at baseline and after treatment with ketoprofen.

Methods: Eight healthy volunteers underwent two 90-minute [11C]PS13 PET scans (injected activity 743±37 MBq) at baseline and at least two hours after oral administration of ketoprofen (75 mg). During each scan, the radiometabolite-corrected arterial input function was measured. VT values were obtained with both a two-tissue compartmental model (2TCM) and Logan graphical analysis.

Results: Brain radioactivity concentration peaked at about 3 minutes after [11C]PS13 injection, with SUV values of 2.9±0.7 at baseline and 3.3±0.8 after ketoprofen treatment. The time-activity curve for parent radiotracer in plasma had a higher peak after ketoprofen treatment (12.5±5.1 SUV) than at baseline (7.5±2.0 SUV). 2TCM analysis fitted the brain time-activity curves well at both baseline and after ketoprofen treatment (SE <5%). VT values were 2.7±0.5 at 1.6±0.5 for baseline and after treatment, respectively. The Lassen plot revealed an occupancy of 80% by ketoprofen and a VND of 1.4. Whole brain BPND was calculated at 1.3.

Conclusion: [11C]PS13 binds specifically to COX-1 in the human brain and can be blocked by the selective inhibitor ketoprofen.

Scientific Focus Area: Molecular Biology and Biochemistry

This page was last updated on Monday, September 25, 2023