Evaluation of Two Potent and Selective PET Radioligands to Image COX-1 and COX-2 in Rhesus Monkeys
Evaluation of Two Potent and Selective PET Radioligands to Image COX-1 and COX-2 in Rhesus Monkeys
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DOI：
10.2967/jnumed.118.211144
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发表时间：
2018-12-01
影响因子：
9.3
通讯作者：
Innis, Robert B.
中科院分区：
文献类型：
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作者：
Kim, Min-Jeong;Shrestha, Stal S.;Innis, Robert B.
本研究评估了新开发的PET放射配体C-11-PS13和C-11-MC1能否分别成像恒河猴体内环氧化酶(COX)-1和COX-2的组成水平。方法：静脉注射两种放射性配体后，进行24次全身PET扫描。为了测量酶特异性摄取，在给予COX-1或COX-2优先的非放射性药物后，也对2种放射性配体进行扫描。同时采集静脉标本，测定母体放射配体浓度。suv从10到90分钟计算。结果：C-11-PS13在脾脏、胃肠道、肾脏和脑等大多数器官均有特异性摄取，可被COX-1阻断，而COX-2则不能。除了卵巢和可能的肾脏外，没有在任何器官中观察到C-11-MC1的特异性摄取。结论：研究结果表明，C-11-PS13在猴子中有足够的信号，可以证明其延伸到人类受试者。相比之下，C-11-MC1不太可能在健康的人身上显示出显著的信号，尽管它可能在炎症条件下这样做。
This study assessed whether the newly developed PET radioligands C-11-PS13 and C-11-MC1 could image constitutive levels of cyclooxygenase (COX)-1 and COX-2, respectively, in rhesus monkeys. Methods: 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. Results: C-11-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-11-MC1 was not observed in any organ except the ovaries and possibly kidneys. Conclusion: The findings suggest that C-11-PS13 has adequate signal in monkeys to justify its extension to human subjects. In contrast, C-11-MC1 is unlikely to show significant signal in healthy humans, though it may be able to do so in inflammatory conditions.