Jannasch Katharina, Dullin Christian, Heinlein Christina, Krepulat Frauke, Wegwitz Florian, Deppert Wolfgang, Alves Frauke
Department of Hematology and Oncology, University Medicine Göttingen, Göttingen, Germany.
Int J Cancer. 2009 Jul 1;125(1):62-70. doi: 10.1002/ijc.24332.
Transgenic mouse models offer an excellent opportunity for studying the molecular basis of cancer development and progression. Here we applied flat-panel volume computed tomography (fpVCT) to monitor tumor progression as well as the development of tumor vasculature in vivo in a transgenic mouse model for oncogene-induced mammary carcinogenesis (WAP-T mice). WAP-T mice develop multiple mammary carcinomas on oncogene induction within 3 to 5 months. Following induction, 3-dimensional fpVCT data sets were obtained by serial single scans of entire mice in combination with iodine containing contrast agents and served as basis for precise measurements of tumor volumes. Thereby, we were able to depict tumors within the mammary glands at a very early stage of the development. Tumors of small sizes (0.001 cm(3)) were detected by fpVCT before being palpable or visible by inspection. The capability to determine early tumor onset combined with longitudinal noninvasive imaging identified diverse time points of tumor onset for each mammary carcinoma and different tumor growth kinetics for multiple breast carcinomas that developed in single mice. Furthermore, blood supply to the breast tumors, as well as blood vessels around and within the tumors, were clearly visible over time by fpVCT. Three-dimensional visualization of tumor vessels in high resolution was enhanced by the use of a novel blood pool contrast agent. Here, we demonstrate by longitudinal fpVCT imaging that mammary carcinomas develop at different time points in each WAP-T mouse, and thereafter show divergent growth rates and distinct vascularization patterns.
转基因小鼠模型为研究癌症发生和发展的分子基础提供了绝佳机会。在此,我们应用平板容积计算机断层扫描(fpVCT)在一种用于癌基因诱导性乳腺癌发生的转基因小鼠模型(WAP-T小鼠)中监测体内肿瘤进展以及肿瘤脉管系统的发育。WAP-T小鼠在癌基因诱导后3至5个月内会发生多发性乳腺癌。诱导后,通过对整个小鼠进行系列单次扫描并结合含碘造影剂获得三维fpVCT数据集,并以此作为精确测量肿瘤体积的基础。由此,我们能够在肿瘤发育的非常早期阶段描绘乳腺内的肿瘤。fpVCT在肿瘤可触及或通过检查可见之前就检测到了小尺寸(0.001 cm³)的肿瘤。确定早期肿瘤发生的能力与纵向无创成像相结合,确定了每例乳腺癌的不同肿瘤发生时间点以及单只小鼠体内发生的多个乳腺癌的不同肿瘤生长动力学。此外,通过fpVCT可随时间清晰地观察到乳腺肿瘤的血液供应以及肿瘤周围和内部的血管。使用新型血池造影剂增强了对肿瘤血管的高分辨率三维可视化。在此,我们通过纵向fpVCT成像证明,每只WAP-T小鼠中的乳腺癌在不同时间点发生,此后显示出不同的生长速率和独特的血管生成模式。