title: Comparison of microwave and magnetic nanoparticle hyperthermia radiosensitization in murine breast tumors.
abstract: 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. Recentin vivostudies (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) / cm3into 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.
authors.affiliation: Dartmouth Medical School, 1 Rope Ferry Road, Hanover, NH, USA 03755 ; Thayer School of Engineering, Dartmouth College, 8000 Cummings Hall, Hanover, NH USA 03755.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Giustini
authors.affiliation: Thayer School of Engineering, Dartmouth College, 8000 Cummings Hall, Hanover, NH USA 03755.
authors.forename: Alicia A
authors.initials: AA
authors.lastname: Petryk
authors.affiliation: Dartmouth Medical School, 1 Rope Ferry Road, Hanover, NH, USA 03755 ; Thayer School of Engineering, Dartmouth College, 8000 Cummings Hall, Hanover, NH USA 03755.
authors.forename: P Jack
authors.initials: PJ
authors.lastname: Hoopes
keywords: AMF; Hyperthermia; intracellular hyperthermia; microwave; nanoparticle; radiation; radiosensitization