Application of High Amplitude Alternating Magnetic Fields for Heat Induction of Nanoparticles Localized in Cancer

Abstract

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.

An induction heating device using planar coil with high amplitude alternating magnetic fields for magnetic hyperthermia

“…Induction heating devices for generating an AMF generally use a ferromagnetic core structure or induction coil structure [4][5][6][7]. The devices employing ferromagnetic core have been used in clinical experiments [6][7][8] but it is difficult for them to further improve the frequency and intensity of the AMF due to the large volume of the core and significant self-heating inside it.…”

“…The devices employing ferromagnetic core have been used in clinical experiments [6][7][8] but it is difficult for them to further improve the frequency and intensity of the AMF due to the large volume of the core and significant self-heating inside it. With smaller volume and less self-heating, the induction coil, which generally based on resonant inverters, was used and researched more and more frequently [5,[9][10][11].…”

Nanomedicine: towards development of patient-friendly drug-delivery systems for oncological applications

“…64 Ivkov et al reported the feasibility of applying high-amplitude AMF to treat cancer tissue with embedded magnetic NPs in 39 female BALB/c athymic nude mice and observed no adverse effects in mice exposed to AMF amplitudes of #700 Oe but mice exposed to AMF amplitudes in excess of 950 Oe experienced morbidity and injury. 72 Preclinical studies on various types of cancer using magnetic hyperthermia have been reported to have promising tumor responses in mouse models. These studies have been pursued independently by different research teams for breast, prostate, and brain tumor models.…”

Local moderate magnetically induced hyperthermia using an implant formed in situ in a mouse tumor model

“…radius of exposed region [32], can lead to distant painful hot spots that would limit the values of f and H, and thus the heating possibilities. The AMF used here is associated with (H Á f ) values ranging from 10Á10 8 to 13.5Á10 8 A/(mÁs) for 9 mT (7.2 kA/m) and 12 mT (9.6 kA/m), at 141 kHz.…”

“…(H Á f ) values higher than 20Á10 8 A/m/s have been used in and ex vivo [37,38]. Pulses of very high amplitude have been experimentally used in mice [32].…”