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. GBM expresses the integrin ¿v¿3 in abundance. We have developed a targeted nanoparticle that can bind to this integrin and deliver therapeutic agents directly to these tumor vessles. By complexing a suicide gene (mutated Raf gene (NP-ATP¿-Raf)) to this nanoparticle, we have successfully treated orthotopic rat brain tumor models. This gene disrupts the VEGF and FGF mediated signaling pathways that result in endothelial cell apoptosis. Significant tumor regression and long term survival have been observed on the rat RT2 and C6 tumor models. Because this approach destroys tumor vessels, we expect a drop in the oxygenation of the tumor in response to treatment and would like to follow the time course of changes that occur after treatment using in vivo MRI techniques. 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 with the treatment of our anti-angiogenic nanoparticle as compared to untreated contols. Methods RT2 (Rat glioma cell line) cells were implanted intracranially in male Fisher Rats. They were divided to two groups. Treated groups (Group 1) received the therapeutic nanoparticles. Control groups (Group 2) received saline. Another control group (Group 3) consist of normal animals without tumor or treatment. T2-weighted MR is performed to obtain the tumor size. T1 mapping oxymetry is then performed to evaluate the oxygenation at different stages of tumor progression.