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Cancer Res:新型成像技术助力癌症研究治疗

2014年11月18日 讯 /生物谷BIOON/ --刊登在过国际杂志Cancer Research上的一篇研究论文中,来自达特茅斯Geisel医学院的研究人员开发了一种新型的荧光成像技术,其可以不在活组织检查的情况下精确鉴别出靶向癌症疗法的特殊受体。

研究者Kimberley S. Samkoe教授说道,蛋白质的过度表达往往是特殊癌症的一个标志,而且也常常在临床肿瘤学领域通过检测肿瘤来用于开发癌症患者的个体化疗法;蛋白质的表达可以通过对肿瘤组织的总蛋白分析测得,而本文中新型技术的开发可以帮助研究者在不进行侵入性活检的情况下精确鉴别出蛋白质受体的含量。

研究者开发的这种双重追踪体内受体浓度成像(RCI)技术包括同时注射靶向和非靶向的成像制剂,随后研究者对5种肿瘤组织的蛋白表达进行了研究,将RCI测得的数据同临床免疫组化所的的数据进行比较,结果显示,通过RCI测得的蛋白质表达和组织分析所得到的结果具有较强的关联性,常用于测定蛋白质表达的技术,比如蛋白印迹或流式细胞计数等,其和RCI值并无关联性。

Samkoe表示,通过分子靶向疗法或诊断成像制剂精确测定肿瘤蛋白受体的含量可以有效改善肿瘤患者的预后,文章中我们开发的体内受体浓度成像技术是一种新型的荧光成像技术,其可以潜在影响对病人肿瘤状态及恶性肿瘤组织分类的临床评估。下一步研究人员将在显微水平下对患者的肿瘤组织进行分析研究来将蛋白受体的表达同不同的生理学特性联系起来,比如和细胞活力、细胞类型、血管分布及总的肿瘤架构等。(生物谷Bioon.com)

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Quantitative in vivo immunohistochemistry of epidermal growth factor receptor using a receptor concentration imaging approach

Kimberley S. Samkoe1,*, Kenneth M Tichauer2, Jason R. Gunn3, Wendy A. Wells4, Tayyaba Hasan5, and Brian W. Pogue3

As receptor-targeted therapeutics become increasingly used in clinical oncology, the ability to quantify protein expression and pharmacokinetics in vivo is imperative to ensure successful individualized treatment plans. Current standards for receptor analysis are performed on extracted tissues. These measurements are static and often physiologically irrelevant, therefore, only a partial picture of available receptors for drug targeting in vivo is provided. Until recently, in vivo measurements were limited by the inability to separate delivery, binding, and retention effects but this can be circumvented by a dual-tracer approach for referencing the detected signal. We hypothesized that in vivo receptor concentration imaging (RCI) would be superior to ex vivo immunohistochemistry. Using multiple xenograft tumor models with varying epidermal growth factor receptor (EGFR) expression, we determined the EGFR concentration in each model using a novel targeted agent (anti-EGFR affibody-IRDye800CW conjugate) along with a simultaneously delivered reference agent (control affibody-IRDye680RD conjugate). The RCI-calculated in vivo receptor concentration was strongly correlated with ex vivo pathologist-scored immunohistochemistry and computer-quantified ex vivo immunofluorescence. In contrast, no correlation was observed with ex vivo Western blot or in vitro flow cytometry assays. Overall, our results argue that in vivo RCI provides a robust measure of receptor expression equivalent to ex vivo immuno-staining, with implications for use in non-invasive monitoring of therapy or therapeutic guidance during surgery.

关键词:成像技术,癌症,肿瘤组织,表皮生长因子,受体,含量

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