Abstract: Our laboratory recently developed [11C]PS13 as a positron emission tomography (PET) radioligand to selectively measure cyclooxygenase-1 (COX-1). The COX enzyme family converts arachidonic acid into prostaglandins and thromboxanes, which mediate inflammation. The total brain uptake of [11C]PS13, which is composed of both target and background binding, can be accurately quantified with gold standard methods of compartmental modeling. This study sought to quantify the specific binding of [11C]PS13 to COX-1 in healthy human brain using scans performed with arterial input function at baseline and after blockade by the COX-1 selective inhibitor ketoprofen.
Methods: Eight healthy volunteers underwent two 90-minute [11C]PS13 PET scans with radiometabolite-corrected arterial input function, at baseline and about two hours after oral administration of ketoprofen (75 mg).
Results: Two-tissue compartment modeling effectively identified the total uptake of radioactivity in brain (as distribution volume (VT)), showing highest densities in the hippocampus, occipital cortex, and the banks of the central sulcus. All brain regions exhibited displaceable/specific binding and, thus, none could be used as a reference region. Ketoprofen blocked ~84% of the binding sites on COX-1 in the whole brain. After extrapolating to full occupancy, the average whole brain values (mL • cm-3) of [11C]PS13 were: specific uptake (VS)=1.6±0.8; background uptake (VND)=1.7±0.6; and target to background ratio (BPND)=1.1±0.5. The hippocampus had the highest BPND value (2.7±0.9). Conclusion: [11C]PS13 exhibited high specific binding to COX-1 in the human brain, but its quantification requires arterial blood sampling.

Data:
Group 1: Eight healthy volunteers (five females and three males, 38.7±7.1 y, 73.4±16.6 kg) participated in this study (NCT04396873). All participants were medically healthy based on medical history, medical records, physical examination, blood laboratory tests, and electrocardiogram. No participants had taken any non-steroidal anti-inflammatory drugs (NSAIDs) for at least two weeks or aspirin for four weeks before the PET scans. All participants gave written informed consent. Study procedures were approved by the NIH Institutional Review Board.

Group 2: Four additional subjects received a test-retest scan, and these were included in the dataset as well.