Objective: Magnetic nanoparticles conjugated to a monoclonal antibody can be i.v. injected to target cancer tissue and will rapidly heat when activated by an external alternating magnetic field (AMF). The result is necrosis of the microenvironment provided the concentration of particles and AMF amplitude are sufficient. High-amplitude AMF causes nonspecific heating in tissues through induced eddy currents, which must be minimized. In this study, application of highamplitude, confined, pulsed AMF to a mouse model is explored with the goal to provide data for a concomitant efficacy study of heating i.v. injected magnetic nanoparticles. Methods: Thirty-seven female BALB/c athymic nude mice (5-8 weeks) were exposed to an AMF with frequency of 153 kHz, and amplitude (400-1,300 Oe), duration (1-20 minutes), duty (15-100%), and pulse ON time (2-1,200 seconds). Mice were placed in a water-cooled four-turn helical induction coil. Two additional mice, used as controls, were placed in the coil but received no AMF exposure. Tissue and core temperatures as the response were measured in situ and recorded at 1-second intervals. Results: No adverse effects were observed for AMF amplitudes of V700 Oe, even at continuous power application (100% duty) for up to 20 minutes. Mice exposed to AMF amplitudes in excess of 950 Oe experienced morbidity and injury when the duty exceeded 50%. Conclusion: High-amplitude AMF (up to 1,300 Oe) was well tolerated provided the duty was adjusted to dissipate heat. Results presented suggest that further tissue temperature regulation can be achieved with suitable variations of pulse width for a given amplitude and duty combination.These results suggest that it is possible to apply high-amplitude AMF (>500 Oe) with pulsing for a time sufficient to treat cancer tissue in which magnetic nanoparticles have been embedded.

In this paper, we describe a modified solenoid coil that efficiently generates high amplitude alternating magnetic fields (AMF) having field uniformity (≤10%) within a 125-cm3 volume of interest. Two-dimensional finite element analysis (2D-FEA) was used to design a coil generating a targeted peak AMF amplitude along the coil axis of ~100 kA/m (peak-to-peak) at a frequency of 150 kHz while maintaining field uniformity to >90% of peak for a specified volume. This field uniformity was realized by forming the turns from cylindrical sections of copper plate and by adding flux concentrating rings to both ends of the coil. Following construction, the field profile along the axes of the coil was measured. An axial peak field value of 95.8 ± 0.4 kA/m was measured with 650 V applied to the coil and was consistent with the calculated results. The region of axial field uniformity, defined as the distance over which field ≥90% of peak, was also consistent with the simulated results. We describe the utility of such a device for calorimetric measurement of nanoparticle heating for cancer therapy and for magnetic fluid hyperthermia in small animal models of human cancer.

Purpose: We describe a modified Helmholtz induction coil, or Maxwell coil, that generates alternating magnetic fields (AMF) having field uniformity ( 10%) within a ¼ 3000 cm 3 volume of interest for magnetic hyperthermia research. Materials and methods: Two-dimensional finite element analysis (2D-FEA) was used for electromagnetic design of the induction coil set and to develop specifications for the required matching network. The matching network and induction coil set were fabricated using best available practices and connected to a 120 kW industrial induction heating power supply. System performance was evaluated by magnetic field mapping with a magnetic field probe, and tests were performed using gel phantoms. Results: Tests verified that the system generated a target peak AMF amplitude along the coil axis of $35 kA/m (peak) at a frequency of 150 ± 10 kHz while maintaining field uniformity to >90% of peak for a volume of $3000 cm 3 . Conclusions: The induction coil apparatus comprising three independent loops, i.e., Maxwell-type improves upon the performance of simple solenoid and Helmholtz coils by providing homogeneous flux density fields within a large volume while minimizing demands on power and stray fields. Experiments with gel phantoms and analytical calculations show that future translational research efforts should be devoted to developing strategies to reduce the impact of nonspecific tissue heating from eddy currents; and, that an inductor producing a homogeneous field has significant clinical potential for deep-tissue magnetic fluid hyperthermia. ARTICLE HISTORY

Purpose -The purpose of this paper is to continue studies previously reported with the primary focus of optimizing an inductor design. The potential benefits of hyperthermia for cancer therapy, particularly metastatic cancers of the prostate, may be realized by the use of targeted magnetic nanoparticles that are heated by alternating magnetic fields (AMFs). Design/methodology/approach -To further explore the potential of this technology, a highthroughput cell culture treatment system is needed. The AMF requirements for this research present challenges to the design and manufacture of an induction system because a high flux density field at high frequency must be created in a relatively large volume. Additional challenges are presented by the requirement that the inductor must maintain an operating temperature between 35 and 398C with continuous duty operation for 1 h or longer. Results of simulation and design of two devices for culture samples and for in vitro tests of multiple samples in uniform field are described. Findings -The inductor design chosen provides a uniform distribution of relatively high magnetic field strength while providing an optimal reduction in the voltage and power requirement. Through development of design and selection of magnetic concentrator, the exposure of the cell cultures to the heat generated by the inductor is minimized. Originality/value -This method of generating uniform high AC magnetic fields in a large volume is beneficial for the study of hyperthermia in cells for a high throughput, necessary for cancer treatment research.

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