Precision magnetic hyperthermia by integrating magnetic particle imaging

Precision magnetic hyperthermia by integrating magnetic particle imaging Magnetic activation of magnetic iron oxide nanoparticles (MIONPs) offers considerable potential for numerous biomedical applications. Approved clinical applications include contrast enhancement for magnetic resonance imaging (MRI) and magnetic fluid hyperthermia (MFH) for cancer treatment. MIONPs are T2 negative contrast agents which have been clinically available for MRI since the late 1980s where very low tissue concentrations (<100 g Fe/g tissue) are needed for imaging. MFH is a powerful nanotechnology-based treatment that enhances radiation therapy (RT). It comprises local heating of tissue by activating MIONPs with an external alternating magnetic field (AMF), enabling treatment anywhere in the body. Human clinical trials demonstrated benefits of MFH for prostate cancer; and, overall survival benefits with RT in recurrent glioblastoma (GBM) resulted in European approval in 2010. However, current MFH effectiveness is limited by the inability to visualize MIONP distribution during MFH, resulting in poor AMF control of MIONP heating, reduced therapeutic efficacy, and unwanted off-target toxicity. An integrated MIONP imaging-MFH technology that provides spatial control of the MFH treatment volume will substantially advance the clinical use of theranostic MIONPs. Magnetic particle imaging (MPI) is an emerging imaging technology that directly quantitates MIONP concentration in tissue with similar or greater sensitivity as MRI. The main magnet in an MPI scanner produces a strong magnetic field gradient containing a region where the magnetic field is approximately zero, i.e. the Field Free Region (FFR). MIONPs in the FFR are magnetically unsaturated and can produce a signal in a receiver coil, while MIONPs elsewhere are magnetically saturated and produce no signal. Images are produced by rastering the FFR across the sample. The FFR used for imaging can be used to localize MFH. By applying a magnetic field gradient and AMF, only MIONPs inside the FFR will heat while MIONPs outside the FFR are saturated and do not heat. MPI and MFH are compatible enabling mm-precision spatial control of MFH. Our objective is to develop an integrated MPI/MFH workflow that incorporates imaging-guided treatment planning with optimal theranostic MIONPs for preclinical biomedical research with small animal (mouse and rat) models. We aim to achieve our objectives by purchasing a HYPER AMF system that will be used with our recently acquired Momentum MPI scanner (funded by a S10 shared instrumentation grant). Our specific aims are: (Aim 1) Identify MIONPs having ideal physical and magnetic properties for MPI/MFH; (Aim 2) Develop MPI-guided MFH treatment using computational modeling and amplitude modulation; (Aim 3) Demonstrate increased therapeutic efficacy of theranostic MPI/MFH in vivo. While the primary objective of the proposed effort is technology development, successful completion of the aims will provide biomedical researchers the ability to realize theranostic applications with magnetic nanoparticles.