T1 OXYMETRY ON HIGH GRADE BRAIN TUMOR WITH ANTIANGIOGENIC THERAPY

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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. Glioblastoma multiforme (GBM) is a malignant brain tumor whose development depends on angiogenesis. We have developed a cationic antiangiogenic nanoparticle (NP) with ¿v¿3 ligand that targets tumor endothelial cells expressing the integrin ¿v¿3. GBMs have been shown to contain high expression of this integrin on their vessels. This therapeutic NPs carries a mutated Raf gene (NP-ATP¿-Raf) complex. This gene disrupts the VEGF and FGF mediated signaling pathway that results in cell apoptosis. Significant tumor regression and long term survival have been observed on rat RT2 tumor model under treatment using this therapeutic nanoparticle. Molecular oxygen (O2) is paramagnetic. Its presence in the tissue changes the longitudinal relaxation rate R1 of hydrogen NMR. R1 exhibits a linear relationship with the partial pressure of O2 (pO2). Thus we can determine Delta pO2 by measuring Delta R1. Recently, a fast T1 mapping method was developed which can obtain a multi-slice T1 map in just a few seconds, making dynamic mapping along a time course feasible. It is shown that this method can quantify the oxygenation change in the brain between the resting and functionally activated states in a motor-visual task. The purpose of this study was to perform T1 oxymetry measurement to investigate how the oxygenation level is altered along the tumor progression with the treatment of our antiangiogenic nanoparticle. Methods Male Fisher Rats with RT2 (Rat glioma cell line) cells implanted intracranially at the age of 8-10 weeks are divided to two groups. Treated group (Group 1) will receive the therapeutic nanoparticles. Control group (Group 2) will receive saline. Another control group (Group 3) with normal animals without tumor and treatment will also be used. T2-weighted MR will be performed to obtain the tumor size. T1 mapping oxymetry will be performed to evaluate the oxygenation at different stages of tumor progression.