Yoshio Ikehata

Heating characteristics of ferromagnetic iron oxide nanoparticles for magnetic hyperthermia

Heating characteristics of Fe oxide nanoparticles designed for hyperthermia were examined. Samples with coercive forces from 50 to 280 Oe(codoped magnetite) were produced with a coprecipitation technique following by hydrothermal reaction. The maximum specific loss powers (SLPs) of 420 W/g was obtained at 117 kHz (640 Oe) for a dispersant sample with coercive force of 280 Oe (ATH9D). SLPs measured on dry powder samples at 17 kHz and measured at 117 kHz on dispersant samples were compared. The measured SLP amplitudes are lower for 17 kHz and higher for 117 kHz than those expected from ferromagnetic dc minor loops. For the 117 kHz case, friction of particles in a carrier fluid (similar mechanism to Brown relaxation in superparamagnetic dispersant samples) is considered to contribute to the heating mechanism.

Selective induction hyperthermia following transcatheter arterial embolization with a mixture of nano-sized magnetic particles (ferucarbotran) and embolic materials: feasibility study in rabbits.

PurposeTo evaluate the possibility of selective hyperthermia following transcatheter arterial embolization (TAE) with ferucarbotran using a newly developed inductive heating (IH) device.Materials and methodsTwelve Japanese white rabbits were separated into four groups: those treated with TAE using a mixture of ferucarbotran and lipiodol (F-L group); those treated with ferucarbotran and gelatin sponge powder; those treated with saline and lipiodol; and a control group. These four groups received IH. Nine rabbits with renal VX2 carcinoma were separated into three groups: IH after TAE (IH-TAE tumor), TAE without IH (TAE tumor), and no treatment (control tumor). The temperature of the tumor was kept at 45°C for 20 min. The therapeutic effect was pathologically evaluated by TUNEL staining.ResultsIn the heating rates of the kidney, the F-L group showed significantly greater values than the group in which iron was not used. In the IH-TAE tumor group, tumors could be selectively heated. In TUNEL staining, the IH-TAE tumor and TAE tumor groups showed significantly greater values of apoptosis rate than in the control tumor group.ConclusionIH following TAE with a mixture of ferucarbotran and lipiodol was capable of inducing selective hyperthermia with our device. However, further investigation is needed to confirm its safety and effectiveness in the treatment of malignant neoplasms in humans.

Minimally required heat doses for various tumour sizes in induction heating cancer therapy determined by computer simulation using experimental data

Purpose: Although induction heating cancer therapy (IHCT) using magnetic nanoparticles can be a promising approach to treatment-less multi-nodular cancers, the objective requirement for successful clinical application has not clearly been elucidated. We intended to define objective heat doses suitable for IHCT, especially focusing on the sizes of liver cancer nodules. Materials and methods: Alternating magnetic fields were applied to three human pancreatic cancer cell lines, the intercellular space of those cell pellets were filled with magnetic nanoparticles, and confirmed the cytotoxic effect of IHCT. Subsequently, the temperatures of liver cancer nodules in IHCT were simulated using a computer software program and the required heat dose for various sized tumours were determined. Results: Heating the cancer cells up to 50°C for 10 min was sufficient for complete cell killing and the heat dose of 1.7 W/gtumour is required for 10 mm tumour. Larger tumours require a smaller heat dose, e.g. 20 mm and 40 mm tumours require 0.7 W/gtumour and 0.6 W/gtumour, respectively, whereas smaller tumours require large amounts of heat, e.g. 5 mm and 1 mm tumours require 5.1 W/gtumour and 105 W/gtumour, respectively. Conclusions: Integrating the presently available technologies, including high-quality magnetic nanoparticles (1000 W/gmaterial) and effective drug delivery systems (1–2 mgmaterial/gtumour), treatment of a 10 mm tumour seems possible. Since treatment of smaller tumours less than 5 mm require substantial heat dose, researchers involved in IHCT should target cancer nodules of 10 mm or more, and develop a heat delivery system providing a minimum of 1.7 W/gtumour.

Complex comprised of dextran magnetite and conjugated cisplatin exhibiting selective hyperthermic and controlled-release potential.

We developed a dextran-magnetite conjugated cisplatin (DM-Cis) complex for use in thermal ablation and as a chemotherapeutic drug. To produce DM-Cis we reacted Cis with 1 mL DM (56 mg/mL iron). The temperature rise of DM-Cis was measured in vitro and in vivo under a portable induction-heating (IH) device. Platinum desorption from DM-Cis over 24 hours was measured in bovine serum. In in vivo accumulation and magnet and exothermic experiments we used four rat groups. In group 1 we delivered DM-Cis intraperitoneally (ip) and placed magnets subcutaneously (sc). In group 2 we injected saline (ip) and placed magnets (sc). In group 3 we injected DM-Cis (ip) and placed a sc incision (sham). The control (group 4) received an ip injection of saline. Rectus abdominis muscle tissue was stained with hematoxylin-eosin and iron-stained tissue areas (μm2) were calculated. The maximum platinum concentration in DM-Cis was approximately 105.6 μg/mL. Over 24 hours, 33.48% of platinum from DM-Cis was released. There was a significant difference (P < 0.05) in the iron-stained area between group 1 and the other groups. The temperature in muscle tissue registered a maximum of 56°C after about 4 min. DM-Cis may represent a magnetically-accumulated anticancer drug with hyperthermic effects.

Antitumor effects of inductive hyperthermia using magnetic ferucarbotran nanoparticles on human lung cancer xenografts in nude mice

Background The effects of inductive hyperthermia on lung cancer have yet to be fully investigated. Magnetic nanoparticles used in inductive hyperthermia are made-to-order and expensive. This study was performed to investigate the use of ferucarbotran in inductive hyperthermia and to clarify whether inductive hyperthermia using ferucarbotran promotes antitumor effects in vivo using a lung cancer cell line. Methods We injected A549 cells subcutaneously into the right thighs of BALB/c nu/nu nude mice. Forty mice with A549 xenografts were then classified into three groups. Group 1 was the control group. All mice in groups 2 and 3 had ferucarbotran injected into their tumors, and mice in group 3 were then subjected to alternating magnetic field irradiation. We evaluated tumor temperature during the hyperthermic procedure, the time course of tumor growth, histologic findings in tumors after hyperthermic treatment, and adverse events. Results Intratumor temperature rose rapidly and was maintained at 43°C–45°C for 20 minutes in an alternating magnetic field. Tumor volumes in groups 1 and 2 increased exponentially, but tumor growth in group 3 was significantly suppressed. No severe adverse events were observed. Histologic findings for the tumors in group 3 revealed mainly necrosis. Conclusion Inductive hyperthermia using ferucarbotran is a beneficial and promising approach in the treatment of lung cancer. Ferucarbotran is a novel tool for further development of inductive hyperthermia.

Development of new cancer treatment using approved MRI contrast agent and induction heating device

MRI contrast agents, Feridex and Resovist have superparamagnetic substance as an active ingredients. Feridex does not show temperature rise under AC magnetic field. In contrast Resovist shows temperature rise under the same condition. W e simulated the optimum frequency on Resovist using phantom and found it is 140 kHz. However treatable cancer volume was limited to 9cm3. We tried a fractionation of Resovist. One of the fractions was found to be effective by more than 6 times compared to the drug by itself. This result suggests that the hyperthermia in combination with the fraction and induction heating device is a promising treatment for cancer.