Significance: Fluorocoxib D, N-[(rhodamin-X-yl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetamide, is a water-soluble optical imaging agent to detect cyclooxygenase-2 (COX-2)-expressing cancer cells. Aim: We evaluated the pharmacokinetic and safety properties of fluorocoxib D and its ability to detect cancer cells in vitro and in vivo. Approach: Pharmacokinetic parameters of fluorocoxib D were assessed from plasma collected at designated time points after intravenous administration of 1 mg / kg fluorocoxib D in six research dogs using a high-performance liquid chromatography analysis. Safety of fluorocoxib D was assessed for 3 days after its administration using physical assessment, complete blood count, serum chemistry profile, and complete urinalysis in six research dogs. The ability of fluorocoxib D to detect COX-2-expressing cancer cells was performed using human 5637 cells in vitro and during rhinoscopy evaluation of specific fluorocoxib D uptake by canine cancer cells in vivo. Results: No evidence of toxicity and no clinically relevant adverse events were noted in dogs. Peak concentration of fluorocoxib D (114.8 ± 50.5 ng / ml) was detected in plasma collected at 0.5 h after its administration. Pretreatment of celecoxib blocked specific uptake of fluorocoxib D in COX-2-expressing human 5637 cancer cells. Fluorocoxib D uptake was detected in histology-confirmed COX-2-expressing head and neck cancer during rhinoscopy in a client-owned dog in vivo. Specific tumor-to-normal tissue ratio of detected fluorocoxib D signal was in an average of 3.7 ± 0.9 using Image J analysis. Conclusions: Our results suggest that fluorocoxib D is a safe optical imaging agent used for detection of COX-2-expressing cancers and their margins during image-guided minimally invasive biopsy and surgical procedures.

中文翻译：

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氟考昔 D 的药代动力学特征，一种用于检测癌症的环加氧酶 2 靶向光学显像剂。

意义：氟考昔 D，N-[(罗丹明-X-基)丁-4-基]-2-[1-(4-氯苯甲酰基)-5-甲氧基-2-甲基-1H-吲哚-3-基]乙酰胺, 是一种水溶性光学显像剂，用于检测表达环氧合酶-2 (COX-2) 的癌细胞。目的：我们评估了氟考昔 D 的药代动力学和安全特性及其在体外和体内检测癌细胞的能力。方法：使用高效液相色谱分析，在六只研究犬中静脉给予 1 mg/kg 氟考昔 D 后，在指定时间点收集的血浆中评估氟考昔 D 的药代动力学参数。在六只研究犬中使用物理评估、全血细胞计数、血清化学特征和完整的尿液分析在给药后 3 天内评估了氟考昔 D 的安全性。氟考昔 D 检测表达 COX-2 的癌细胞的能力是在体外使用人 5637 细胞进行的，并且在鼻镜检查期间对犬癌细胞在体内的特定氟考昔 D 摄取进行了评估。结果：在犬中未发现毒性证据和临床相关不良事件。在给药后 0.5 小时采集的血浆中检测到氟考昔 D 的峰值浓度 (114.8 ± 50.5 ng/ml)。塞来昔布的预处理阻止了表达 COX-2 的人类 5637 癌细胞中氟考昔 D 的特异性摄取。在客户拥有的狗的体内鼻镜检查期间，在组织学证实的表达 COX-2 的头颈癌中检测到氟考昔 D 摄取。使用 Image J 分析，检测到的氟考昔 D 信号的特定肿瘤与正常组织的比率平均为 3.7 ± 0.9。结论：