Comparison of Folate Receptor Targeted Optical Contrast Agents for Intraoperative Molecular Imaging.
Comparison of Folate Receptor Targeted Optical Contrast Agents for Intraoperative Molecular Imaging.
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DOI：
10.1155/2015/469047
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Singhal S
中科院分区：
文献类型：
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作者：
De Jesus E;Keating JJ;Kularatne SA;Jiang J;Judy R;Predina J;Nie S;Low P;Singhal S
背景资料。术中成像可以识别癌细胞，以提高手术切除率，因此荧光造影剂应运而生。我们的目标是对两种荧光染料EC17和OTL38进行临床前比较，这两种染料都针对叶酸受体，但具有不同的荧光染料。材料。用HeLa和KB细胞株在体外和体内比较EC17和OTL38的亮度、敏感性、药代动力学和生物分布。然后在小鼠身上进行活体实验。结果。EC17和OTL38的最大激发和发射波长分别为470/520 nm和774/794 nm。在体外，与EC17相比，OTL38需要更长的孵育时间才能获得最大荧光；然而，在60分钟内，峰值信号背景比(SBR)是EC17的1.4倍(p<；0.001)。此外，OTL38改进了用于检测较小数量细胞的SBR。在体内，与EC17相比，使用OTL38显示的肿瘤的SBR平均改善了3.3倍(范围为1.48-5.43)。在动物研究中，这两种染料都没有引起明显的毒性。结论。在临床前测试中，与EC17相比，OTL38似乎具有更高的灵敏度和亮度。这与人们普遍认为的近红外(NIR)染料比可见波长荧光染料更少的自发荧光和散射问题不谋而合。
Background. Intraoperative imaging can identify cancer cells in order to improve resection; thus fluorescent contrast agents have emerged. Our objective was to do a preclinical comparison of two fluorescent dyes, EC17 and OTL38, which both target folate receptor but have different fluorochromes. Materials. HeLa and KB cells lines were used for in vitro and in vivo comparisons of EC17 and OTL38 brightness, sensitivity, pharmacokinetics, and biodistribution. In vivo experiments were then performed in mice. Results. The peak excitation and emission wavelengths of EC17 and OTL38 were 470/520 nm and 774/794 nm, respectively. In vitro, OTL38 required increased incubation time compared to EC17 for maximum fluorescence; however, peak signal-to-background ratio (SBR) was 1.4-fold higher compared to EC17 within 60 minutes (p < 0.001). Additionally, the SBR for detecting smaller quantity of cells was improved with OTL38. In vivo, the mean improvement in SBR of tumors visualized using OTL38 compared to EC17 was 3.3 fold (range 1.48–5.43). Neither dye caused noticeable toxicity in animal studies. Conclusions. In preclinical testing, OTL38 appears to have superior sensitivity and brightness compared to EC17. This coincides with the accepted belief that near infrared (NIR) dyes tend to have less autofluorescence and scattering issues than visible wavelength fluorochromes.