Journal of Neuro-Oncology 56: 233–239, 2002. © 2002 Kluwer Academic Publishers. Printed in the Netherlands. Laboratory Investigation Effective solitary hyperthermia treatment of malignant glioma using stick type CMC-magnetite. In vivo study Takanari Ohno 1 , Toshihiko Wakabayashi 1 , Atsuhito Takemura 1 , Jun Yoshida 1 , Akira Ito 2 , Masashige Shinkai 2 , Hiroyuki Honda 2 and Takeshi Kobayashi 2 1 Department of Neurosurgery, Nagoya University School of Medicine, Showa-ku, Nagoya, Japan; 2 Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya, Japan Key words: hyperthermia, malignant glioma, magnetite, carboxymethylcellulose, CMC-magnetite Summary Various kinds of hyperthermic treatment for malignant glioma had been inhibited due to both their incomplete feverish action and strict cooling effect of the brain. The author shows an effective results of hyperthermia for the treatment of malignant glioma in an in vivo study using stick type carboxymethylcellulose (CMC)-magnetite, a newly manufactured magnetite-product. A stick type CMC-magnetite, containing magnetite particles, was inserted into the T-9 glioma in the rat brain stereotactically, and the rats were exposed to an alternative magnetic field (AMF). The application time of AMF, which measured 88.9 kHz and 380 Oe, was 30 min a day. The rats were divided into three groups: three AMF applications (group I), one AMF application (group II) and no application but only injection of CMC-magnetite (control). As a result, the mean survival in days of these three groups measured 44.2 ± 10.9 (group I), 17.0 ± 1.5 (group II) and 14.4 ± 1.5 (control). This investigation showed both significant effectiveness in attacking malignant glioma and significant prolonging of the survival time in rats. It is also a characteristic feature of the magnetite particles to spread through the tumor diffusely after three applications of AMF. This feature seemed to be one of the main factors that caused greater hyperthermic effect on glioma in this study. This method of hyperthermic treatment could be a useful strategy in the treatment of malignant glioma. Introduction Clinically, despite the various methods of hyperthermia having been developed and applied to malignant glioma, it still shows a miserable prognosis. Although, previously, some contrived methods of hyperthermia using such devices as an implant heating system [1] and interstitial microwave microantenna [2–4] indi- cated partial tumor reduction, significant prolonging of survival time has rarely been reported in an in vivo study, especially with sole hyperthermia. We devel- oped some products made of magnetite particles, and applied them to the tumor, both intracranially and extracranially. This strategy, using magnetite particles, is based on the heat radiation associated with the physical process of hysteresis loss of magnetic sub- stance in the alternative magnetic field (AMF). In particular, magnetite cationic liposome (MCL), which is easily absorbed into the tumor cell due to its cationic charge, could produce an effective hyperther- mic condition as with the intracellular hyperthermia in the in vitro studies [5–8]. An extracranial tumor implanted subcutaneously in a rat’s femoral region dis- appeared completely in this manner [5]. Furthermore, we manufactured another magnetite-product, which is a thin stick-type mingled with carboxymethylcellu- lose (CMC) to obtain higher heat effect. This product has several features, such as ease of manipulation and improved ability to target the correct point in the brain, as well as having a higher concentration of magnetite (3.3 mg of Fe 3 O 4 /5.7 μl). The author tried hyperthermic attack using this type of CMC-magnetite against malig- nant glioma in rats and significant results, including prolonging of survival time of rats with T-9 glioma and complete disappearance of the tumor, were confirmed and evaluated statistically.