血管生成拟态（VM）是血管之外的另一种肿瘤微循环体系，是抗肿瘤药物研究的新兴重要靶点。目前评价抗VM药物仅采用细胞生物学和组织病理学方法，药物抑制VM的体内作用过程尚缺少在体、动态评价。而正电子发射断层成像（PET）技术能通过靶向、可视化描述体内特定生物标志物的分布和活性，动态、定量表征生物学过程和药效。本项目拟采用针对VM重要生物标志物（基质金属蛋白酶-2和上皮酪氨酸受体激酶A2）的寡肽类正电子示踪剂，对VM研究中经典的裸鼠移植黑色素瘤模型进行PET成像，通过测定肿瘤的示踪剂摄取水平，在体、实时、定量、可视化表征上述标志物的活性，并采用组织病理学方法予以验证；应用上述PET方法和已知可抑制黑色素瘤VM的模型药物沙利度胺，建立在体、动态评价抗VM药物的影像学方法，表征沙利度胺对黑色素瘤VM的作用规律。本项目的完成将为以VM为靶点的抗肿瘤药物筛选、药效学和临床疗效评价研究提供新的方法学思路。

Vasculogenic mimicry (VM) is a unique type of micro-circulation network inside solid tumor with overall difference from blood vessel, and VM has become a rising and important target in the development of anti-cancer drug. Currently, there are only cell-biological and histo-pathological methods available for the evaluation of anti-VM drug. In vivo and dynamic method for characterizing the process of inhibitory Effect on VM is still required. Positron emission tomography (PET) can monitor biological process and drug effect quantitatively and dynamically, by characterizing the distribution and activity of specific biomarker in a targeted and visual way. In this program, we plan to execute the PET imaging on hetero-xenograft node mouse melanoma model that is classical in VM research, using positron emission nuclide-labelled oligo-peptide tracers that target key biomarkers, such as matrix metalloproteinase-2 (MMP-2) and erythropoietin-producing hepatocellular tyrosine kinase A2 (EphA2), involved in the formation of VM. By quantifying the uptake level of the tracers in tumor, the activity of MMP-2/EphA2 will be evaluated in vivo, in real-time and quantitatively. These results will be validated by histo-pathological assay. Based On these PET method and model drug thalidomide which is able to inhibit VM in melanoma, through investigating the interventional progress of thalidomide on VM in melanoma, an imaging method for the evaluation of inhibitory effect of anti-VM drug will be developed. If this program is implemented, methodological complement would be offered to the researches of anti-tumor drug screening, pharmacodynamics and clinical response, in which VM are focus on.