This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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