Department of Biological Sciences, 100 Galvin Life Sciences Center, University of Notre Dame, Notre Dame, IN 46556, USA.
Curr Mol Med. 2013 Mar;13(3):368-76. doi: 10.2174/1566524011313030006.
Tumor heterogeneity is recognized as a major issue within clinical oncology, and the concept of personalized molecular medicine is emerging as a means to mitigate this problem. Given the vast number of cancer types and subtypes, robust pre-clinical models of cancer must be studied to interrogate the molecular mechanisms involved in each scenario. In particular, mouse models of tumor metastasis are of critical importance for pre-clinical cancer research at the cancer cell molecular level. In many of these experimental systems, tumor cells are injected intravenously, and the distribution and proliferation of these cells are subsequently analyzed via ex vivo methods. These techniques require large numbers of animals coupled with time-consuming histological preparation and analysis. Herein, we demonstrate the use of two facile and noninvasive imaging techniques to enhance the study of a pre-clinical model of breast cancer metastasis in the lung. Breast cancer cells were labeled with a near-infrared fluorophore that enables their visualization. Upon injection into a living mouse, the distribution of the cells in the body was detected and measured using whole animal fluorescence imaging. X-ray computed tomography (CT) was subsequently used to provide a quantitative measure of longitudinal tumor cell accumulation in the lungs over six weeks. A nuclear probe for lung perfusion, 99mTc-MAA, was also imaged and tested during the time course using single photon emission computed tomography (SPECT). Our results demonstrate that optical fluorescence methods are useful to visualize cancer cell distribution patterns that occur immediately after injection. Longitudinal imaging with X-ray CT provides a convenient and quantitative avenue to measure tumor growth within the lung space over several weeks. Results with nuclear imaging did not show a correlation between lung perfusion (SPECT) and segmented lung volume (CT). Nevertheless, the combination of animal models and noninvasive optical and CT imaging methods provides better research tools to study cancer cell differences at the molecular level. Ultimately, the knowledge gleaned from these improved studies will aid researchers in uncovering the mechanisms mediating breast cancer metastasis, and eventually improve the treatments of patients in the clinic.
肿瘤异质性被认为是临床肿瘤学中的一个主要问题，个性化分子医学的概念正在出现，作为缓解这一问题的一种手段。鉴于癌症类型和亚型的数量众多，必须研究强大的癌症临床前模型，以研究每种情况下涉及的分子机制。特别是，肿瘤转移的小鼠模型对于癌症细胞分子水平的临床前癌症研究至关重要。在许多这些实验系统中，肿瘤细胞通过静脉内注射，然后通过离体方法分析这些细胞的分布和增殖。这些技术需要大量的动物，并且需要进行耗时的组织学准备和分析。在这里，我们展示了两种简便且非侵入性的成像技术在增强肺转移临床前乳腺癌模型研究中的应用。用近红外荧光团标记乳腺癌细胞，使其能够可视化。将细胞注射到活鼠体内后，使用全身荧光成像技术检测和测量细胞在体内的分布。随后使用 X 射线计算机断层扫描（CT）提供六周内肺部肿瘤细胞纵向积累的定量测量。还使用单光子发射计算机断层扫描（SPECT）在时间过程中对肺灌注的核探针 99mTc-MAA 进行成像和测试。我们的结果表明，光学荧光方法可用于可视化注射后立即发生的癌细胞分布模式。X 射线 CT 的纵向成像为测量数周内肺部肿瘤生长提供了一种方便且定量的方法。核成像的结果并未显示肺灌注（SPECT）与分割肺容积（CT）之间的相关性。尽管如此，动物模型和非侵入性光学和 CT 成像方法的结合为研究分子水平的癌细胞差异提供了更好的研究工具。最终，从这些改进的研究中获得的知识将有助于研究人员揭示介导乳腺癌转移的机制，并最终改善临床患者的治疗效果。
