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In-vivo fluorescence detection of breast cancer growth factor receptors by fiber-optic probe

机译:光纤探针在体内荧光检测乳腺癌生长因子受体

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Breast cancer treatment options often include medications that target the overexpression of growth factor receptors, such as the proto-oncogene human epidermal growth factor receptor 2 (HER2eu) and epidermal growth factor receptor (EGFR) to suppress the abnormal growth of cancerous cells and induce cancer regression. Although effective, certain treatments are toxic to vital organs, and demand assurance that the pursued receptor is present at the tumor before administration of the drug. This requires diagnostic tools to provide tumor molecular signatures, as well as locational information. In this study, we utilized a fiber-optic probe to characterize in vivo HER2 and EGFR overexpressed tumors through the fluorescence of targeted dyes. HER2 and EGFR antibodies were conjugated with ICG-Sulfo-OSu and Alexa Fluor 680, respectively, to tag BT474 (HER2+) and MDA-MB-468 (EGFR+) tumors. The fiber was inserted into the samples via a 30-gauge needle. Different wavelengths of a supercontinuum laser were selected to couple into the fiber and excite the corresponding fluorophores in the samples. The fluorescence from the dyes was collected through the same fiber and quantified by a time-correlated single photon counter. Fluorescence at different antibody-dye concentrations was measured for calibration. Mice with subcutaneous HER2+ and/or EGFR+ tumors received intravenous injections of the conjugates and were later probed at the tumor sites. The measured fluorescence was used to distinguish between tumor types and to calculate the concentration of the antibody-dye conjugates, which were detectable at levels as low as 40 nM. The fiber-optic probe presents a minimally invasive instrument to characterize the molecular signatures of breast cancer in vivo.
机译:乳腺癌的治疗选择通常包括针对生长因子受体过度表达的药物,例如原癌基因人表皮生长因子受体2(HER2 / neu)和表皮生长因子受体(EGFR),以抑制癌细胞的异常生长和导致癌症消退。尽管有效,但是某些治疗对重要器官有毒性,并要求确保在给药前肿瘤中存在被追踪的受体。这需要诊断工具来提供肿瘤分子特征以及位置信息。在这项研究中,我们利用光纤探针通过靶向染料的荧光来表征体内HER2和EGFR过表达的肿瘤。 HER2和EGFR抗体分别与ICG-Sulfo-OSu和Alexa Fluor 680偶联,以标记BT474(HER2 +)和MDA-MB-468(EGFR +)肿瘤。经由30号针将纤维插入样品中。选择不同波长的超连续谱激光器耦合到光纤中,并激发样品中相应的荧光团。来自染料的荧光通过同一根光纤收​​集,并通过与时间相关的单光子计数器进行定量。测量了不同抗体染料浓度下的荧光以进行校准。患有皮下HER2 +和/或EGFR +肿瘤的小鼠接受了静脉注射的结合物,随后在肿瘤部位进行了探测。所测量的荧光用于区分肿瘤类型并计算抗体-染料偶联物的浓度,可在低至40 nM的水平检测到。光纤探针提供了一种微创仪器,用于表征体内乳腺癌的分子特征。

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