Development of a prototype clinical theranostic platform combining Magnetic Particle Imaging (MPI) and Magnetic Fluid Hyperthermia (MFH) for the treatment of brain tumors - SUMMARY/ABSTRACT
In this SBIR grant proposal, “Development of a prototype clinical theranostic platform combining Magnetic
Particle Imaging (MPI) and Magnetic Fluid Hyperthermia (MFH) for the treatment of brain tumors” we will develop
a human brain-sized, integrated localized MFH/MPI system. We will develop an imaging-guided MFH treatment
device capable of closed-loop localized heating and tomographic temperature monitoring during treatment.
MFH relies on the delivery of magnetic nanoparticles to tumors followed by application of alternating magnetic
fields, which causing local heating of tissue and killing of tumor cells. Cell death occurs due to the heat or by
enhancing the cytotoxic effects of radio/chemotherapy. MFH offers considerable potential for numerous
biomedical applications, especially as an adjunct to radiation therapy in the clinical treatment of recurrent
glioblastoma. However, MFH currently suffers from limitations that persist after nearly four decades of clinical
experience and regulatory approval in Europe. Following delivery, the nanoparticle distribution within the tumor
can be heterogeneous and unpredictable, leading to undertreatment in areas of low MNP concentration, and
excessive heating near normal tissues. These issues are compounded by a limited ability to accurately monitor
tissue temperature in 3D and in realtime.
The technology developed in this SBIR constitutes a paradigm shift for MFH by developing the first human-
sized localized MFH system. Localized MFH is a new technology that uses strong magnetic field gradients to
confine MNP heating to a small region. Particles within the region can generate heat, while those outside the
region cannot. Our technology will transition clinical MFH from the current state of the art of loosely targeted,
regional heating to mm-accurate localized heating of target tissues. We believe this transition from regional to
precisely targeted is comparable to the transition of early, loosely targeted radiation therapy to the present day,
3D-targeted intensity-modulated radiation therapy.
In this Direct to Phase II SBIR proposal, we will add MFH to our existing clinical-scale MPI prototype to enable
localized MPI/MFH with integrated temperature sensing, and validate the performance in animal cadavers
through the following specific aims:
Aim 1. Build a clinical RF heating head coil for simultaneous MFH and imaging and integrate it into our
prototype clinical imager
Aim 2. Integrate MPI-based temperature sensing with heating to control MFH to a treatment plan.
Aim 3. Test overall system in phantoms and animal cadavers in preparation for preclinical trials in dogs
At the end of this Direct to Phase II proposal, we will have demonstrated integrated MPI/MFH for precisely
localized image-guided therapeutic heating in a prototype that is suitable for clinical studies. In our future work,
we plan to test this system in a large animal trial at JHU for treatment of spontaneous canine GBM.
