Abstract 5567: Development of a novel magnetic anti-cancer drug for hyperthermic therapy.

Abstract

Abstract Background: Hyperthermic therapy is a type of cancer treatment in which body tissue is exposed to high temperature (up to 113°F). Despite of its effectiveness, it has not been widely used. One reason is that it is technically difficult to increase high temperature only in a target cancer site. To address this issue, we have developed a novel nano-magnetic particle, i.e., EI236. EI236 exhibits not only anti-cancer effect, but also ferromagnetic property. Because of its magnetism, this drug can generate heat by itself when it is exposed to an alternating current magnetic field (ACMF). Method: We established a rabbit model of VX2 cells (rabbit osteosarcoma) grafted on legs to examine the anti-cancer and hyperthermal effects of EI236 in vivo. Rabbits were divided into five groups; 1) no treatment group 2) intra-venous (iv.) EI236 injection group 3) intra-arterial (ia.) EI236 group 4) ia. Methotrexate (MTX) injection group, and 5) ia. EI236+ACMF group. The volume of tumor was measured daily, and then the samples were harvested and evaluated histologically by HE, Ki67, and TUNEL staining. Results: The effect of EI236 was similar to that of MTX when EI236 was injected via intra-arterial infusion. Via intra-arterial infusion was more effective than iva intra-venous infusion. When EI236 was injected and the tumor was exposed to ACMF for simultaneous chemotherapeutic and hyperthermal effects, it showed the greatest regression of tumor among all the groups examined. EI236 significantly increased necrosis as determined by HE staining, and further increased it by ACMF. Similarly, EI236 decreased cell proliferation as determined by Ki67, and further decreased it by ACMF. Moreover EI236 increased apoptosis as determined by TUNEL staining, and further increased it by ACMF. These results demonstrated that the exposure of ACMF greatly enhanced the anti-cancer effect of EI236. Taken together, EI236 exhibited simultaneous effects of anti-cancer and thyperthermia. Conclusion: These results demonstrate that EI236 can provide us in developing a new strategy of simultaneous hyperthermo-chemotherapy in the future. Citation Format: Masanari Umemura, Hidenobu Fukumura, Itaru Sato, Xianfeng Feng, Haruki Eguchi, Yoshihiro Ishikawa. Development of a novel magnetic anti-cancer drug for hyperthermic therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5567. doi:10.1158/1538-7445.AM2013-5567