Abstract

Imaging of Malignant Brain Tumors with Multifunctional Dendrimer-based Nanoparticles

Meser Ali, Senior Staff Investigator, Director, Cellular and Molecular Imaging Lab, Department of Neurology, Henry Ford Hospital

Malignant brain tumors are among the most devastating tumors, with survival of only one to three years after diagnosis even with the best of treatments. Treatment of brain tumor faces a unique challenge compare to other cancer types, due to the fact that not only are brain tumors developed within bone-covered structures thereby having restricted space to expand, but they are also embedded deeply within an organ which carries a multitude of vital functions. Hence, even a benign tumor can be life-threatening if it is an area of the brain that controls critical body functions such as breathing or blood circulation. Invasive biopsy is routinely utilized to assess histological type, classification, grade and potential aggressiveness of brain cancer and also for determination of the type of drug regimen employed for treatment. Imaging techniques include CT, PET, ultrasound and, most importantly, MRI. For some brain tumors the delineation of the actual tumor volume is difficult because peritumoral edema does not readily allow precise discrimination of tumor margins. Surgery and radiation therapy (followed by adjuvant chemotherapy) very often fail because of uncertainty in delineating the tumor margins. Therefore, as pointed out by the experts in the field, successful therapeutic approaches would depend on developing high quality imaging modalities. Thus, although the past decade has seen dramatic advances in surgical modalities and development of novel molecular target-based adjuvant therapies for brain tumors, a significant improvement in patient outcome has yet to be realized. This suggests that, in order to decrease the morbidity associated with malignant brain tumors, paradigm-changing modalities for detection and cure of cancer are urgently needed. Nanoparticles have drawn increased interest in treating malignant brain tumors due to their potential to act as a vector for brain delivery and to provide tumor specific detection and treatment. Multifunctional nanoparticles can be engineered into a single nanoplatform and hold great promise for brain tumor diagnosis and treatment. We have demonstrated that the intravenously administered dendrimer-based dual modal nanopartilces are able to traverse pores of the blood-brain tumor barrier of U251 malignant glioma. Therefore, spherical dendrimer-based multifunctional nanoparticles ranging between 4 to 10 nm in diameter will be presented with the potential applications in malignant brain tumors imaging with a compromised blood brain tumor barrier.