Comparative Study of Extracellular and Intracellular Magnetic Hyperthermia Treatments Using Magnetic Particle Imaging

Abstract

The purpose of this study was to evaluate the effectiveness of intracellular magnetic hyperthermia treatment (MHT) in comparison with that of extracellular MHT using magnetic particle imaging (MPI). Colon-26 cells were implanted subcutaneously into the backs of 8-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm 3 , the mice were divided into control (n = 10), extracellular MHT (n = 8), and intracellular MHT groups (n = 7). In the control group, MHT was not performed. In the extracellular MHT and intracellular MHT groups, the tumors were injected directly with magnetic nanoparticles (MNPs) (400 mM Resovist®) and were heated for 20 min using an alternating magnetic field. During MHT, the temperatures of the tumor and rectum were measured using optical fiber thermometers. In the extracellular MHT group, MHT was performed 15 min after the injection of MNPs, whereas MHT was performed one day after the injection of MNPs in the intracellular MHT group. In both groups, MPI images were obtained using our MPI scanner immediately before, immediately after, and 7 and 14 days after MHT. After the MPI studies, we drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels within the ROI. Transmission electron microscopic (TEM) images were also obtained from resected tumors. In all groups, tumor volume was measured every day and the relative tumor volume growth (RTVG) was calculated. The TEM images showed that almost all the MNPs were aggregated in the extracellular space in the extracellular MHT group, whereas they were contained within the intracellular space in the intracellular MHT group. Although the temperature of the tumor in the intracellular MHT group was significantly lower than that in the extracellular MHT group, the RTVG value in the intracellular MHT group was significant- ly lower than that in the control group 2 days or more after MHT and that in the extracellular MHT group 3, 4, and 5 days after MHT. The average MPI value normalized by that immediately before MHT in the intracellular MHT group was significantly higher than that in the extracellular MHT group immediately and 7 days after MHT. The maximum and total MPI values normalized by those immediately before MHT in the intracellular MHT group were significantly higher than those in the extracellular MHT group 7 days after MHT, suggesting that the temporal change of MNPs within the tumor in the intracellular MHT group was smaller than that in the extracellular MHT group. Our results suggest that intracellular MHT is more cytotoxic than extracellular MHT in spite of a lower temperature rise of tumors, and that MPI is useful for evaluating the difference in the temporal change of MNPs in the tumor between extracellular MHT and intracellular MHT.

Micron-sized iron oxide particles for both MRI cell tracking and magnetic fluid hyperthermia treatment

“…In vitro , magnetic hyperthermia using ScreenMAG particles was remarkably efficient in inducing cell death after 1 h. Moreover, intracellular ScreenMAG are more cytotoxic than extracellular ScreenMAG. This result is in agreement with a previous study 39 . Since the temperature elevation ranged between 43 and 50 °C for intracellular ScreenMAG, the cell death is probably apoptosis as described in Cortie et al 40 .…”

Nanoclusters of crystallographically aligned nanoparticles for magnetic thermotherapy: aqueous ferrofluid, agarose phantoms andex vivomelanoma tumour assessment

“…To understand whether or not this affects the therapeutic outcome further experiments are needed. It is worth mentioning that it was recently shown that cell death induced in vivo on colon tumours after application of MH treatment occurred without a significant global temperature increase 60 .…”

Magnetic particle imaging for radiation-free, sensitive and high-contrast vascular imaging and cell tracking

“…We note that the theranostic potential of MPI extends far beyond guiding cell-based treatments. Although this review focuses on MPI imaging applications, extensive work has also been performed demonstrating the utility of MPI for ionizing radiation-free surgical guidance 34–37 and therapeutic guidance, such as with magnetic hyperthermia 38–42 .…”