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Comparison of Folate Receptor Targeted Optical Contrast Agents for Intraoperative Molecular Imaging

机译:叶酸受体靶向光学造影剂在术中分子成像中的比较。

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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 forin vitroandin vivocomparisons of EC17 and OTL38 brightness, sensitivity, pharmacokinetics, and biodistribution.In vivoexperiments 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.
机译:背景。术中影像学可以识别癌细胞以改善切除率;因此出现了荧光造影剂。我们的目标是对两种荧光染料EC17和OTL38进行临床前比较,它们均靶向叶酸受体但具有不同的荧光染料。将HeLa和KB细胞系用于EC17和OTL38亮度,敏感性,药代动力学和生物分布的体外和体内比较,然后在小鼠中进行体内实验。 EC17和OTL38的峰值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,峰峰值信噪比(SBR)是EC17的1.4倍(p <0.001)。此外,OTL38改善了用于检测少量细胞的SBR。在体内,与EC17相比,使用OTL38可视化的肿瘤SBR的平均改善是3.3倍(范围1.48–5.43)。两种染料均未在动物研究中引起明显的毒性。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。这与公认的观点相吻合,即与可见波长的荧光染料相比,近红外(NIR)染料往往具有较少的自发荧光和散射问题。

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