Design, Synthesis, and Evaluation of an 18F-Labeled Radiotracer Based on Celecoxib-NBD for Positron Emission Tomography (PET) Imaging of Cyclooxygenase-2 (COX-2)
Design, Synthesis, and Evaluation of an 18F-Labeled Radiotracer Based on Celecoxib-NBD for Positron Emission Tomography (PET) Imaging of Cyclooxygenase-2 (COX-2)
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DOI：
10.1002/cmdc.201500287
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发表时间：
2015-10-01
期刊：
影响因子：
3.4
通讯作者：
Wuest, Frank
中科院分区：
文献类型：
--
作者：
Kaur, Jatinder;Tietz, Ole;Wuest, Frank
基于已报道的荧光考克斯-2显像剂塞来昔布-NBD（3; NBD=7-硝基苯并呋咱），设计并合成了一系列新型含氟环氧合酶-2（考克斯-2）抑制剂。体外考克斯-1/考克斯-2抑制数据显示，N-（4-氟苄基）-4-（5-对甲苯基-3-三氟甲基吡唑-1-基）苯磺酰胺（5; IC 50 = 0.36 M，SI>277）和N-氟甲基-4-（5-对甲苯基-3-三氟甲基吡唑-1-基）苯磺酰胺（6; IC 50 = 0.24 M，SI>416）是有效和选择性的考克斯-2抑制剂。选择化合物5用短寿命正电子发射体氟-18（F-18）进行放射性标记，并作为正电子发射断层扫描（PET）成像剂进行评价。使用人结肠直肠癌模型HCA-7在体外和体内分析放射性示踪剂[F-18]5。尽管放射性示踪剂摄取到表达考克斯-2的HCA-7细胞中是高的，但没有发现考克斯-2特异性结合的证据。
A series of novel fluorine-containing cyclooxygenase-2 (COX-2) inhibitors was designed and synthesized based on the previously reported fluorescent COX-2 imaging agent celecoxib-NBD (3; NBD=7-nitrobenzofurazan). In vitro COX-1/COX-2 inhibitory data show that N-(4-fluorobenzyl)-4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide (5; IC50=0.36M, SI>277) and N-fluoromethyl-4-(5-p-tolyl-3-trifluoromethylpyrazol-1-yl)benzenesulfonamide (6; IC50=0.24M, SI>416) are potent and selective COX-2 inhibitors. Compound 5 was selected for radiolabeling with the short-lived positron emitter fluorine-18 (F-18) and evaluated as a positron emission tomography (PET) imaging agent. Radiotracer [F-18]5 was analyzed in vitro and in vivo using human colorectal cancer model HCA-7. Although radiotracer uptake into COX-2-expressing HCA-7 cells was high, no evidence for COX-2-specific binding was found. Radiotracer uptake into HCA-7 tumors in vivo was low and similar to that of muscle, used as reference tissue.