Magnetic particles (magnetite) were used to make radiofrequency (RF) capacitive hyperthermia effective to a specific site. In an agar phantom experiment, a magnetite-containing agar piece was buried in a large agar phantom and heated by an 8 MHz-RF capacitive heating device. The magnetite-containing agar piece was heated more than the magnetite-free agar phantom, and the specific adsorption rate in the phantom was increased 1.5 times by the magnetite particles. The temperature distribution in the large agar phantom showed that the highest temperature was obtained at the center of the magnetite-containing piece. The rate of temperature increase was approximately proportional to the magnetite concentration to the power 0.8. This method was applied to an in vivo experiment using a pig. Magnetite was prepared as a colloidal material dispersed in a carboxymethylcellulose solution (CMC-Mag) and intramuscularly injected in the pig femur. As a result of 8 MHz-RF heating, the temperature at the CMC-Mag-injected point increased to over 43°C after 7 min, while the temperature at a point without magnetite was under 40°C at the same time. The specific adsorption rate in the magnetite-containing tissue was twice that of the magnetite-free tissue. In addition, the time required to reach a temperature of over 43°C was only 7 min, while it was over 15 min in the case without the CMC-Mag.

Specific heating of magnetic particles in radiofrequency (RF) capacitive hyperthermia and its hyperthermic effect were investigated in an in vivo study. Magnetite cationic liposomes (MCLs) were injected into a rat tumor on the femur and 8 MHz-RF capacitive heating was applied to the rat under 'mild heating' conditions. Although the input power of RF capacitive heating was low under the same power conditions, the MCLs-injected tumor was heated over 43°C, whereas it was only heated to 41°C in the case of the rats not injected with MCLs. A necrotic area in the tumor was observed in the heated rats. From the results of histological observation of the removed tissue, the necrotic area in the MCLs-injected tumor was wider than that in MCLs-free tumor. Complete tumor suppression was observed in 71% (5/7) of MCLs-injected rats, and the hyperthermic effect was greatly improved by the MCLs.Key words: RF capacitive heating -Magnetic particle -Regional hyperthermia Hyperthermia is a promising approach in cancer therapy and various methods are employed to achieve it.1, 2) However, the inevitable technical problem with hyperthermia is the difficulty of uniform heating of only the tumor region to the required temperature without damaging normal tissue. Therefore, some researchers have proposed inductive heating methods using submicron magnetic particles for hyperthermia. [3][4][5] We have also developed 'magnetite cationic liposomes' (MCLs) for intracellular hyperthermia. [6][7][8] MCLs were developed to improve adsorption and accumulation into the tumor cells and showed ten-fold higher affinity for the tumor cells than neutrally charged magnetoliposomes.6) This is enabled by the electrostatic interaction with the negatively charged cell membrane.9, 10) The hyperthermic effect of the MCLs was examined in vivo. 8)MCLs were directly injected into solid tumors formed subcutaneously in F344 rats and the rats were irradiated three times for 30 min with an alternating magnetic field. An alternating magnetic field with relative low frequency of the order of 100 kHz heated only the tumor containing the MCLs. As a result, complete tumor regression was observed in many rats after the irradiation.Inductive heating using submicron magnetic particles is a superior method as stated above, but it cannot yet be practiced in Japan since magnetic field generators are still in an experimental stage. In Japan, capacitive heating of tumors using a radiofrequency (RF) electric field is a popular heating method and has been clinically used. 11,12) Capacitive heating is, however, not suitable for site-specific hyperthermia, because it is unable to heat tumors specifically. The specific adsorption rate (SAR) of electric field energy depends on the electrical properties of each tissue, such as permittivity and electric resistance. Since the difference in the electrical properties of tumors and normal tissues is not high, it is difficult to heat only the tumor specifically. In order to prevent excessive heating of normal tissue, 'mild' heating condition...

It was shown that alternative magnetic field is generated around ferromagnetic particles in 8 MHz RF electric field and that heat is generated in ferromagnetic particles due to hysteresis loss by the action of alternative magnetic field ; i. e. the same heat generation mechanism with inductive heating.