Project Summary: This proposal describes a five-year research and career development program to prepare
Dr. Hamed Arami for a career as an independent investigator. This program will build upon Dr. Arami’s
multidisciplinary background as a bioengineer scientist, trained in nanomedicine and basic cancer imaging, by
providing expertise in brain cancer biology and image-guided therapy of brain tumors using Magnetic Particle
Imaging (MPI). The PI will be mentored at Stanford Medical School by Drs. Sanjiv S. Gambhir (Main mentor,
basic cancer biology, cancer pathology and cancer nanotechnology), Heike Daldrup-Link (co-mentor, magnetic
nanomedicine, imaging and therapeutics), Max Wintermark (co-mentor, neuroimaging and brain MPI), Melanie
Hayden (co-mentor, neurosurgery and neurology) and Bob Sinclair (co-mentor, nanomaterials characterization).
Treatment of malignant primary brain tumors particularly glioblastoma multiforme (GBM) is challenging because
of GBM resistant to chemotherapy and radiotherapy. Also, there are different types of GBM tumors that are not
operable due to their locations in the brain (e.g. deep brain regions). In addition, routine GBM imaging in clinics
are based on using gadolinium-based magnetic resonance imaging contrast agents. However, using these
gadolinium-based contrast agents raises major concerns for GBM patients suffering from chronic kidney
disease, which can be resolved by using nanoparticle contrast agents that do not show any renal clearance due
to their larger size. The overall goal of the proposed research is to use MPI as a two-armed and high-resolution
approach for safer imaging and magnetothermal therapy of the GBM. Four types of brain tumors with different
levels of aggressiveness will be studied to identify the feasibility of the proposed method in different brain tumor
microenvironments. Recently, I developed methods for tuning iron oxide nanoparticles (NPs) to generate high
resolution (i.e. ~600 µm) MPI images with ultra-high contrast agent mass sensitivity of less than ~550pg Fe/µL.
I have used MPI for three-dimensional targeted imaging of the U87 brain tumors in mice after intravenous
injection of these NPs. Additionally, in separate studies, I demonstrated the feasibility of the MPI for selective
magnetothermal therapy of the U87 tumors, when NPs were directly injected into tumors. In this project, I will
first evaluate MPI and heat generation efficiency of the NPs at different brain depths to further identify ideal NPs
design and imaging criteria for general brain tumor imaging or local magnetothermal therapy with MPI (Aim 1).
Then, I will evaluate MPI for targeted 3D imaging of four different types of intracranially implanted brain tumors
after intravenous injection of the nanoparticles, followed by nanoparticle biodistribution studies (Aim 2). Finally,
I will use intratumoral injection of my tumor-penetrating NPs for MPI-guided magnetothermal therapy of the deep
brain tumors (representative models for inoperable GBM), followed by in-depth survival and neuropathological
studies (Aim 3). Iron oxide nanoparticles have been approved by FDA for several clinical applications and we
hope that this method will ultimately find applications to many other types of solid tumors.