ANTI-ANGIOGENIC PLATFORM FOR IMAGING AND THERAPY

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们已经证明，这里开发的抗血管生成治疗平台可以显著减少大鼠TR 2原位脑肿瘤模型中的肿瘤质量，而不会复发肿瘤生长。由于RT 2不是浸润性模型，我们将这种纳米颗粒治疗平台进一步扩展到C6原位脑肿瘤模型。C6是一种浸润性肿瘤模型，其中单个C6细胞在正常大鼠脑中扩散，如在临床GBM病例中。与RT 2模型相比，使用小分子造影剂Gd（DTPA）的动态对比增强（DCEMR）在C6肿瘤模型中显示出更高的渗透性，表明C6模型具有更高的血管生成潜力。本研究目前的重点是评估在这种浸润模型中的治疗效果。此外，由于该治疗系统中RT 2肿瘤血管系统的破坏具有长期无疾病结局，因此使用小和大（血池）分子量T1造影剂的DCEMR将用于评价图像对治疗的响应的时间变化。该评价对于临床翻译和未来药物开发中的药物设计都很重要。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We have demonstrated that the anti-angiogenic therapeutic platform developed here can significantly reduce tumor mass without recurrence of tumor growth in the TR2 orthotopic brain tumor model in rats. Since RT2 is not an infiltrative model, we have further extended this nanoparticle therapeutic platform to the C6 orthotopic brain tumor model. C6 is an infiltrative tumor model in which individual C6 cells diffuse in the normal rat brain, as in clinical GBM cases. Dynamic contrast enhanced (DCEMR) using small molecule contrast agent Gd(DTPA) has shown a higher permeability in the C6 tumor model compared with the RT2 model, indicating higher angiogenic potential of the C6 model. The current focus of this study is to evaluate the therapeutic efficacy in this infiltrative model. In addition, since the destruction of the RT2 tumor vasculature in this therapeutic system has long-term disease-free outcome, DCEMR with both small and large (bloodpool) molecular weight T1 contrast agents will be used to evaluate temporal changes in images in response to therapy. This evaluation is important both for clinical translation and pharmaceutical design in future drug development.