确定肿瘤靶向治疗受体的新成像技术

　　

生物通报道：随着受体靶向治疗越来越多地用于临床肿瘤学，当务之急是能够量化蛋白质表达和体内药物动力学，以确保成功的个体化治疗方案。当前，受体分析的标准是在提取组织上执行的。这些测量是静态的，往往在生理上是不相关的，因此，只能提供药物靶定可用受体的一部分信息。直到最近，体内测量因无法单独传递、结合和保留而受限。

最近，英国达特茅斯大学的研究人员开发出一种荧光成像技术，可以更准确地确定靶向肿瘤治疗的受体，而无需组织活检。相关研究结果以“Quantitative in vivo immunohistochemistry of epidermal growth factor receptor using a receptor concentration imaging approach”为题，发表在最近的《Cancer Research》杂志。

本文第一作者、Thayer工程学院兼任助理教授、Geisel医学院外科学助理教授Kimberley S. Samkoe指出：“蛋白质的超表达，是某些癌症的一个标志，被用于临床肿瘤学个性化治疗，进行肿瘤检测、分子疗法和治疗监测。蛋白质表达，当前是通过肿瘤组织的总蛋白质分析测量的。这种新技术可让我们准确地确定可用于结合药物的蛋白质受体的数量，而无需侵入性活检。”

研究人员开发出一种双示踪物体内受体浓度成像（receptor concentration imaging，RCI）技术，涉及到同时注射一种靶向和非靶向显像剂。然后他们研究了5份肿瘤的蛋白质表达，将它们的RCI数据，与临床免疫组织化学确定的数据（病理学家在临床上记录或计算机独立分析所得）进行对比。他们发现，RCI所确定的蛋白质表达，与组织分析所确定的蛋白质表达结果密切相关。他们还发现，常用的蛋白质表达测量技术，如Western blots或流式细胞术，与RCI值没有相互关联，而事实上会过分预测可用于治疗或诊断靶定的受体的数量。

Samkoe说：“准确地确定肿瘤中用于分子治疗靶点或诊断性显像剂的蛋白质受体数量，能够大大影响肿瘤患者的预后结果。我们的体内受体浓度成像技术，是一种新型方法，可用于荧光成像，潜在地影响肿瘤状态的临床评估和恶性组织分类。”

Samkoe指出，这项研究着眼于肿瘤内的平均受体表达。下一步将在微观层面研究肿瘤，以将受体表达与不同的生理特征联系起来，例如细胞活力、细胞型、血管质和总的肿瘤结构。

（生物通：王英）

延伸阅读：Lancet：预测前列腺癌复发风险的新方案

生物通推荐原文摘要：
Quantitative in vivo immunohistochemistry of epidermal growth factor receptor using a receptor concentration imaging approach
Abstract: 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.