Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
J Surg Oncol. 2010 Dec 1;102(7):758-64. doi: 10.1002/jso.21735.
The application of fluorescent molecular imaging to surgical oncology is a developing field with the potential to reduce morbidity and mortality. However, the detection thresholds and other requirements for successful intervention remain poorly understood. Here we modeled and experimentally validated depth and size of detection of tumor deposits, trade-offs in coverage and resolution of areas of interest, and required pharmacokinetics of probes based on differing levels of tumor target presentation.
Three orthotopic tumor models were imaged by widefield epifluorescence and confocal microscopes, and the experimental results were compared with pharmacokinetic models and light scattering simulations to determine detection thresholds.
Widefield epifluorescence imaging can provide sufficient contrast to visualize tumor margins and detect tumor deposits 3-5 mm deep based on labeled monoclonal antibodies at low objective magnification. At higher magnification, surface tumor deposits at cellular resolution are detectable at TBR ratios achieved with highly expressed antigens.
A widefield illumination system with the capability for macroscopic surveying and microscopic imaging provides the greatest utility for varying surgical goals. These results have implications for system and agent designs, which ultimately should aid complete resection in most surgical beds and provide real-time feedback to obtain clean margins.
荧光分子成像在肿瘤外科中的应用是一个不断发展的领域，具有降低发病率和死亡率的潜力。然而，成功干预的检测阈值和其他要求仍了解甚少。在这里，我们建立了模型，并通过实验验证了肿瘤沉积物的检测深度和大小、关注区域的覆盖范围和分辨率的权衡以及基于肿瘤靶标不同呈现水平的探针所需的药代动力学。
通过宽场荧光显微镜和共聚焦显微镜对三个原位肿瘤模型进行了成像，并将实验结果与药代动力学模型和光散射模拟进行了比较，以确定检测阈值。
基于标记的单克隆抗体，低物镜放大倍数的宽场荧光成像可以提供足够的对比度来可视化肿瘤边缘并检测 3-5 毫米深的肿瘤沉积物。在更高的放大倍数下，用高表达抗原获得的 TBR 比值可以检测到具有细胞分辨率的表面肿瘤沉积物。
具有宏观检测和微观成像能力的宽场照明系统为不同的手术目标提供了最大的实用性。这些结果对系统和试剂设计具有重要意义，最终应有助于大多数手术床的完全切除，并提供实时反馈以获得干净的边缘。
