Abstract 4576: Development of thermochemotherapy using cisplatin and ferucarbotran (Resovist®) in head and neck cancer
Authors: Sato Itaru , Umemura Masanari , Mitsudo Kenji , Feng Xianfeng , Nakashima Hideyuki , Kioi Mitomu , Miyajima Akiyoshi , Eguchi Haruki , Tohnai Iwai , Ishikawa Yoshihiro 
Published: May 2015

Abstract
Background: Radical surgery for patients with advanced head and neck cancer causes dysfunctions as well as decreases quality of life. To overcome this issue, we developed a new combination therapy of cisplatin and inductive hyperthermia using ferucarbotran (Resovist®). Ferucarbotran, which is made of superparamagnetic iron oxide, generates heat when exposed to an alternating magnetic fields (AMF). Herein, we explored whether ferucarbotran could be used as a heat source for hyperthermia upon exposure to AMF in the presence of cisplatin. Our aim is to evaluate the simultaneous therapeutic efficacy of chemotherapy and inductive hyperthermia for head and neck cancer.
Materials and Methods: OSC-19 and HSC-3, human oral cancer cell lines, were used in this study. Cell proliferation was assessed by methyl thiazolyl tetrazorium (MTT) assay. The intracellular level of reactive oxygen species (ROS) was measured using fluorescent dye 2′, 7′-dichlorodihydrofluorescein diacetate. Apoptotic cells were stained with Annexin V, allophycocyanin conjugate and 7-amino-actinomycin D, and measured by fluorescence activated cell sorting (FACS), to evaluate early and late apoptosis. Thermal images and temperature were obtained by thermograpy and thermometer. Alternating magnetic fields were generated by a transistor-driven vertical coil at a frequency of 308 KHz and electric current (EC) 250 A.
Results: Ferucarbotran generated heat in a dose- and time-dependent manner when exposed to an AMF, suggesting that ferucarbotran could be used as a heat source for hyperthermia. As we expected, Cisplatin suppressed proliferation of OSC-19 and HSC-3 cells in a dose-dependent manner, not only furucarbtran. First, we performed MTT assay and ROS generation assay to evaluate whether hyperthermia effect enhanced anti-cancer effect in the presence of cisplatin. Simply incubation at 42 °C for one hour enhanced the anti-cancer effect and ROS generation in the presence of cisplatin. Cisplatin induced apoptosis of OSC-19 and HSC-3 cells in a dose-dependent manner. Ferucarbotran further promoted cisplatin-induced apoptosis compared to cisplatin alone, when exposed to an AMF for an hour. Thus, the combination of cisplatin with ferucarbotran /AMF was more effective than cisplatin alone, suggesting that we could reduce the amount of cisplatin in clinical usage.
Conclusion: Our findings suggest that combination therapy of cisplatin and ferucarbotran in an AMF may be used to develop a new combination therapy for head and neck cancer.
Citation Format: Itaru Sato, Masanari Umemura, Kenji Mitsudo, Xianfeng Feng, Hideyuki Nakashima, Mitomu Kioi, Akiyoshi Miyajima, Haruki Eguchi, Iwai Tohnai, Yoshihiro Ishikawa. Development of thermochemotherapy using cisplatin and ferucarbotran (Resovist®) in head and neck cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4576. doi:10.1158/1538-7445.AM2014-4576