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magneThermTM What is ~ Magnetic Fluid Hyperthermia Hyperthermia (thermal therapy or thermotherapy) is a type of cancer treatment in which body tissue is exposed to high temperatures (up to 45 °C). Research has shown that high temperatures can damage and kill cancer cells, usually with minimal injury to normal tissues. By killing cancer cells and damaging proteins and structures within cells, hyperthermia may shrink tumors. National Cancer Institute, USA Hyperthermia in cancer therapy is: 1) Heating tumor above 42 oC 2) A physical treatment that could result in fewer side effects than chemotherapy An overview of the process: Malignant cells are more sensitive to the rise in temperature than healthy ones MFH is based on a defined transfer of power onto magnetic nanoparticles in an alternate magnetic field that is determined by the type of particles, frequency and magnetic field strength and which results in local generation of heat. Depending on the equilibrium temperature set in the tumour tissue, this heat may either destroy the tumour cells directly (thermoablation) or result in a synergic reinforcement of radiation/chemo efficacy (hyperthermia). The challenge lies in being able to deliver an adequate quantity of the magnetic particles to generate enough heat in the target using AC magnetic field conditions that are clinically acceptable. Most of the laboratory and animal model based studies reported so far are characterized by the use of magnetic field conditions that could not be safely used with a human patient. In most instances, reducing the field strength or frequency to safer levels would almost certainly lead to such a reduction in the heat output from the magnetic material as to render it useless in this application. It is important therefore to understand the underlying physical mechanisms by which heat is generated in small magnetic particles by alternating magnetic fields. Enough heat must be generated by the particles to sustain tissue temperatures of at least 42˚C for 30 min or so. Calculating the heat deposition rate required to achieve this is complicated by the presence of blood flow and tissue perfusion, both of which are dominant sources of tissue cooling and both of which vary actively as tissue is heated. The frequency and strength of the externally applied AC magnetic field used to generate the heating is limited by deleterious physiological responses to high frequency magnetic. These include stimulation of peripheral and skeletal muscles, possible cardiac stimulation and arrhythmia, and non-specific inductive heating of tissue. Generally, the useable range of frequencies and amplitudes is considered to be f = 0.05–1.2MHz and H = 0–15 kAm−1. nanoTherics Ltd E-mail: [email protected] Tel. + 44 1782 622112 www.nanotherics.com PI-410 Experimental data on exposure to much higher frequency fields comes from groups such as Oleson et al who developed a hyperthermia system based on inductive heating of tissue, and Atkinson et al who developed a treatment system based on eddy current heating of implantable metal thermoseeds. Atkinson et al concluded that exposure to fields where the product H x f does not exceed 4.85 × 108Am−1 s−1 is safe and tolerable for Magnetic Fluid Hyperthermia. The magneTherm™system from nanoTherics has the following capabilities for studies in the field of Magnetic Fluid Hyperthermia; f ( KHz) f (Hz) 110 168 176 262 335 474 523 633 739 987 Ho (kA/m) Ho (A/m) Ho x f 19.9 13.5 18.3 18.3 13.5 8.7 15.9 7.2 12.7 9.5 19,900 13,500 18,300 18,300 13,500 8,700 15,900 7,200 12,700 9,500 2.19 x 109 2.27 x 109 3.22 x 109 4.79 x 109 4.52 x 109 4.12 x 109 8.32 x 109 4.56 x 109 9.39 x 109 9.38 x 109 110,000 168,000 176,000 262,000 262,000 335,000 474,000 523,000 739,000 987,000 The magneTherm™ has the capacity to exceed the safe and tolerable dose quoted above but also has the flexibility to be able to vary the frequency and field strength to deliver medically relevant exposure to nanoparticles, cells (adherent or suspension) and 3D cell structures. Magnetic Field Amplitude vs Votage rms Vp-p Vrms (showing consistent Vrms/mT) 1400.00 1200.00 1000.00 800.00 600.00 400.00 200.00 0.00 mT 2.09 2.09 4.18 4.18 6.26 6.26 8.35 8.35 Vp-p 100 200 300 400 10.44 12.53 14.62 16.70 18.79 20.88 22.97 10.44 12.53 14.62 16.70 18.79 20.88 22.97 500 600 700 800 900 1000 1100 V/ mT 47.89 47.89 47.89 47.89 47.89 47.89 47.89 47.89 47.89 47.89 47.89 25.06 25.06 1200 47.89 Please note: Voltage and therefore Field Strength can be adjusted to required value. nanoTherics Ltd E-mail: [email protected] Tel. + 44 1782 622112 www.nanotherics.com PI-410