Our laboratory recently developed [¹¹C]PS13 as a PET radioligand to selectively measure cyclooxygenase-1 (COX-1). The cyclooxygenase enzyme family converts arachidonic acid into prostaglandins and thromboxanes, which mediate inflammation. The total brain uptake of [¹¹C]PS13, which is composed of both specific binding and background uptake, 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-min [¹¹C]PS13 PET scans with radiometabolite-corrected arterial input function, at baseline and about 2 h after oral administration of ketoprofen (75 mg). Results: Two-tissue compartment modeling effectively identified the total uptake of radioactivity in the brain (as distribution volume), showing the highest densities in the hippocampus, the occipital cortex, and the banks of the central sulcus. All brain regions exhibited displaceable and specific binding, and thus none could be used as a reference region. Ketoprofen blocked approximately 84% of the binding sites on COX-1 in the whole brain. After full occupancy was extrapolated, the average whole-brain values of [¹¹C]PS13 were 1.6 ± 0.8 mL·cm⁻³ for specific uptake, 1.7 ± 0.6 mL·cm⁻³ for background uptake, and 1.1 ± 0.5 for the specific-to-background ratio. The hippocampus had the highest specific-to-background ratio value of 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.

我们的实验室最近开发了 [¹¹C]PS13 作为 PET 放射性配体，用于选择性测量环氧合酶-1 （COX-1）。环氧合酶家族将花生四烯酸转化为前列腺素和血栓素，从而介导炎症。[11 C]PS13 由特异性结合和背景摄取组成，可以用区室建模的金标准方法准确量化 [¹¹C]PS13 的总脑摄取。本研究试图量化 [¹¹C]PS13 与健康人脑中 COX-1 的特异性结合，使用基线时和被 COX-1 选择性抑制剂酮洛芬阻断后用动脉输入功能进行的扫描。方法：8 名健康志愿者在基线和口服酮洛芬 （75 mg） 后约 2 小时接受了两次具有放射性代谢物校正动脉输入功能的 90 分钟 [¹¹C]PS13 PET 扫描。结果：双组织隔室建模有效地确定了大脑中放射性的总摄取量（作为分布体积），显示海马体、枕叶皮层和中央沟两岸的密度最高。所有大脑区域都表现出可置换和特异性结合，因此没有一个可以用作参考区域。酮洛芬阻断了全脑中大约 84% 的 COX-1 结合位点。外推完全占有后，[¹¹C]PS13 的平均全脑值为特异性摄取 1.6 ± 0.8 mL·^cm-3，背景摄取为 1.7 ± 0.6 mL·^cm-3，特异性与背景比为 1.1 ± 0.5。海马体的特异性与背景比值最高，为 2.7 ± 0.9。 结论： [¹¹C]PS13 与人脑中的 COX-1 表现出高度特异性结合，但其定量需要动脉血采样。