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Magnetic Particle Imaging (MPI) for Imaging and Magnetothermal Therapy of Brain Tumors

Award Number: R00CA234208
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/16/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Magnetic Particle Imaging (MPI) for Imaging and Magnetothermal Therapy of Brain Tumors - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2024	ARIZONA STATE UNIVERSITY	1475 N SCOTTSDALE RD STE 200	SCOTTSDALE	AZ	85257	MARICOPA	USA	Cancer Research Manpower	000	5	7/7/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $249,000 )
2024	2024	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Cancer Research Manpower	000	5	7/16/2024	NON-COMPETING CONTINUATION	$249,000
2024	2024	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Cancer Research Manpower	001	5	7/29/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $249,000

Issue Date FY: 2023 ( Subtotal = $325,630 )
2023	2023	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Cancer Research Manpower	002	4	8/9/2023	NON-COMPETING CONTINUATION	$244,020
2023	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Research Manpower	000	3	2/14/2023	EXTENSION WITH OR WITHOUT FUNDS	$0
2023	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Cancer Research Manpower	001	3	6/13/2023	EXTENSION WITH OR WITHOUT FUNDS	$81,610
														Subtotal = $325,630

Issue Date FY: 2022 ( Subtotal = $249,000 )
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Research Manpower	000	3	8/24/2022	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $823,630

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Magnetic Particle Imaging (MPI) for Imaging and Magnetothermal Therapy of Brain Tumors

Award Number: R00CA234208

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/16/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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