Current Challenges in Image-Guided Magnetic Hyperthermia Therapy for Liver Cancer

For patients diagnosed with advanced and unresectable hepatocellular carcinoma (HCC), liver transplantation remains the best option to extend life. Challenges with organ supply often preclude liver transplantation, making palliative non-surgical options the default front-line treatments for many patients. Even with imaging guidance, success following treatment remains inconsistent and below expectations, so new approaches are needed. Imaging-guided thermal therapy interventions have emerged as attractive procedures that offer individualized tumor targeting with the potential for the selective targeting of tumor nodules without impairing liver function. Furthermore, imaging-guided thermal therapy with added standard-of-care chemotherapies targeted to the liver tumor can directly reduce the overall dose and limit toxicities commonly seen with systemic administration. Effectiveness of non-ablative thermal therapy (hyperthermia) depends on the achieved thermal dose, defined as time-at-temperature, and leads to molecular dysfunction, cellular disruption, and eventual tissue destruction with vascular collapse. Hyperthermia therapy requires controlled heat transfer to the target either by in situ generation of the energy or its on-target conversion from an external radiative source. Magnetic hyperthermia (MHT) is a nanotechnology-based thermal therapy that exploits energy dissipation (heat) from the forced magnetic hysteresis of a magnetic colloid. MHT with magnetic nanoparticles (MNPs) and alternating magnetic fields (AMFs) requires the targeted deposition of MNPs into the tumor, followed by exposure of the region to an AMF. Emerging modalities such as magnetic particle imaging (MPI) offer additional prospects to develop fully integrated (theranostic) systems that are capable of providing diagnostic imaging, treatment planning, therapy execution, and post-treatment follow-up on a single platform.