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Hyperthermia has been shown to be an effective radiosensitizer. Its utility as a clinical modality has been limited by a
minimally selective tumor sensitivity and the inability to be delivered in a tumor-specific manner. Recent in vivo studies
(rodent and human) have shown that cancer cell-specific cytotoxicity can be effectively and safely delivered via iron
oxide magnetic nanoparticles (mNP) and an appropriately matched noninvasive alternating magnetic field (AMF). To
explore the tumor radiosensitization potential of mNP hyperthermia we used a syngeneic mouse breast cancer model,
dextran-coated 110 nm hydrodynamic diameter mNP and a 169 kHz / 450 Oe (35.8 kA/m) AMF. Intradermally
implanted (flank) tumors (150 ± 40 mm3) were treated by injection of 0.04 ml mNP (7.5 mg Fe) / cm3 into the tumor and
an AMF (35.8 kA/m and 169 kHz) exposure necessary to achieve a CEM (cumulative equivalent minute) thermal dose
of 60 (CEM 60). Tumors were treated with mNP hyperthermia (CEM 60), radiation alone (15 Gy, single dose) and in
combination. Compared to the radiation and heat alone treatments, the combined treatment resulted in a greater than
two-fold increase in tumor regrowth tripling time (tumor treatment efficacy). None of the treatments resulted in
significant normal tissue toxicity or morbidity. Studies were also conducted to compare the radiosensitization effect of
mNP hyperthermia with that of microwave-induced hyperthermia. The effects of incubation of nanoparticles within
tumors (to allow nanoparticles to be endocytosed) before application of AMF and radiation were determined. This
preliminary information suggests cancer cell specific hyperthermia (i.e. antibody-directed or anatomically-directed
mNP) is capable of providing significantly greater radiosensitization / therapeutic ratio enhancement than other forms of hyperthermia delivery.
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Andrew J. Giustini, Alicia A. Petryk, Paul J. Hoopes, "Comparison of microwave and magnetic nanoparticle hyperthermia radiosensitization in murine breast tumors," Proc. SPIE 7901, Energy-based Treatment of Tissue and Assessment VI, 79010E (22 February 2011); https://doi.org/10.1117/12.876515