Human breast cancer tumor models:: Molecular imaging of drug susceptibility and dosing during HER2/neu-targeted therapy
Human breast cancer tumor models:: Molecular imaging of drug susceptibility and dosing during HER2/neu-targeted therapy
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DOI：
10.1148/radiol.2482071496
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发表时间：
2008-09-01
期刊：
影响因子：
19.7
通讯作者：
Mahmood, Umar
中科院分区：
文献类型：
--
作者：
Gee, Michael S.;Upadhyay, Rabi;Mahmood, Umar
目的：使用近红外（NIR）光学成像评估的治疗敏感性和药物剂量的原位人类乳腺癌植入小鼠治疗molecularly targeted therapy.Materials和方法：这项研究是由机构动物护理和使用委员会批准。通过将人表皮生长因子受体2型（HER 2）特异性抗体曲妥珠单抗与荧光染料缀合来合成成像探针。用流式细胞术评估体外探针结合。将HER 2正常和HER 2过表达的人乳腺癌细胞原位植入裸鼠中。活体激光扫描荧光显微镜用于评估探针与肿瘤细胞的体内缔合。在治疗前或治疗后，对携带3-5 mm直径肿瘤的小鼠静脉内注射0.4 nmol HER 2探针。总共123只小鼠用于所有体内肿瘤生长和成像实验。评估肿瘤荧光强度，并确定标准荧光值。统计学显著性通过进行标准方差分析确定在整个成像cohols.Results：HER 2探针使分化HER 2正常和HER 2过表达的人乳腺癌细胞在体外和体内，与肿瘤曲妥珠单抗敏感性相关的结合水平。曲妥珠单抗治疗前和治疗期间的系列成像显示，（P <0.05），从而在肿瘤生长的总体减少明显之前提供了成功抑制HER 2的早期证据。使用HER 2特异性成像探针的NIR成像能够评估人类乳腺肿瘤的治疗敏感性和HER 2-特异性治疗期间的药物给药。曲妥珠单抗的靶向治疗。这种方法，结合断层成像技术，有可能在临床上确定患者的资格和足够的药物剂量的分子靶向癌症治疗。(C)RSNA，2008年。
Purpose: To use near-infrared (NIR) optical imaging to assess the therapeutic susceptibility and drug dosing of orthotopic human breast cancers implanted in mice treated with molecularly targeted therapy.Materials and Methods: This study was approved by the institutional animal care and use committee. Imaging probes were synthesized by conjugating the human epidermal growth factor receptor type 2 (HER2)-specific antibody trastuzumab with fluorescent dyes. In vitro probe binding was assessed with flow cytometry. HER2-normal and HER2-overexpressing human breast cancer cells were orthotopically implanted in nude mice. Intravital laser scanning fluorescence microscopy was used to evaluate the in vivo association of the probe with the tumor cells. Mice bearing 3-5-mm-diameter tumors were intravenously injected with 0.4 nmol of HER2 probe before or after treatment. A total of 123 mice were used for all in vivo tumor growth and imaging experiments. Tumor fluorescence intensity was assessed, and standard fluorescence values were determined. Statistical significance was determined by performing standard analysis of variance across the imaging cohorts.Results: HER2 probe enabled differentiation between HER2-normal and HER2-overexpressing human breast cancer cells in vitro and in vivo, with binding levels correlating with tumor trastuzumab susceptibility. Serial imaging before and during trastuzumab therapy revealed a significant reduction (P < .05) in probe binding with treatment and thus provided early evidence of successful HER2 inhibition days before the overall reduction in tumor growth was apparent.Conclusion: NIR imaging with HER2-specific imaging probes enables evaluation of the therapeutic susceptibility of human mammary tumors and of drug dosing during HER2-targeted therapy with trastuzumab. This approach, combined with tomographic imaging techniques, has potential in the clinical setting for determining patient eligibility for and adequate drug dosing in molecularly targeted cancer therapies. (C) RSNA, 2008.