Sathy B N, Chou Y H, Li H J, Chang C, Chow K P N
Institute of Biomedical Sciences, Academic Sinica, Taipei, Taiwan, Republic of China.
Lab Anim. 2009 Jan;43(1):53-9. doi: 10.1258/la.2007.007105. Epub 2008 Nov 17.
Accumulating evidence indicates that tumour growth is angiogenesis-dependent. Non-invasive assessment of the relationship between tumour growth and associated angiogenesis is essential for diagnosis and for therapeutic interventions. We utilized a combination of high-resolution T2-weighted and dynamic contrast-enhanced magnetic resonance imaging to investigate the dynamics of angiogenesis during tumour growth in a mouse tumour model expressing Epstein-Barr virus-encoded latent membrane protein 1 isolated from a nasopharyngeal carcinoma in Taiwan. Serial imaging acquisitions were performed starting on the third day after subcutaneous implantation of tumours, through day 28. We observed a progressive increase in tumour volume until day 14, followed by rapid and exponential growth. The volume transfer constant, K(trans), also increased significantly on day 14, and then gradually decreased, suggesting that the angiogenic switching occurs prior to significant tumour growth. At the initial stage, the K(trans) values were significantly higher in the tumour peripheral region than in the tumour core, but, during tumour growth, the K(trans) values in the region between the tumour periphery and core gradually increased, becoming larger than those of the periphery. These results demonstrate that the ability to perform repeated measurements assessing the correlation between tumour growth kinetics and tumour angiogenesis makes it possible to determine the critical time of angiogenic switching prior to rapid tumour growth, as well as suggesting the timing of therapy.
越来越多的证据表明肿瘤生长依赖于血管生成。对肿瘤生长与相关血管生成之间关系进行非侵入性评估对于诊断和治疗干预至关重要。我们利用高分辨率T2加权和动态对比增强磁共振成像相结合的方法，在一个表达从台湾鼻咽癌中分离出的爱泼斯坦-巴尔病毒编码的潜伏膜蛋白1的小鼠肿瘤模型中，研究肿瘤生长过程中血管生成的动态变化。从肿瘤皮下植入后的第三天开始，持续到第28天进行连续成像采集。我们观察到肿瘤体积在第14天之前逐渐增加，随后快速呈指数增长。容积转运常数K(trans)在第14天也显著增加，然后逐渐下降，这表明血管生成转换发生在肿瘤显著生长之前。在初始阶段，肿瘤周边区域的K(trans)值显著高于肿瘤核心区域，但在肿瘤生长过程中，肿瘤周边与核心之间区域的K(trans)值逐渐增加，变得比周边区域的K(trans)值更大。这些结果表明，能够进行重复测量以评估肿瘤生长动力学与肿瘤血管生成之间的相关性，使得在肿瘤快速生长之前确定血管生成转换的关键时间成为可能，同时也为治疗时机提供了建议。
