Heat Dose Based Large Tumor Treatment with Multiple Site Injections of Heat-generating Nanoparticles Dispersible within Tumor Tissue

Abstract

: Solid cancer therapy based on necrosis induction with heat-generating nanoparticles has been developed in Japan. Heat was induced from intratumorally injected magnetite cationic lipid composite particles (MCL particles) by alternating magnetic field irradiations to kill cancer cells nearby located. In our previous report we have showed importance of heat dose index in vivo (J / cm 3 tumor volume) for tumor regression when 45 mg MCL particles were injected at a single site of 1.36 cm 3 tumor. Purpose of this study is to show rationale and utility of multiple site injections of MCL particles for treatment of large tumors more than 1.36 cm 3 . Rat mammary tumors were induced by 7,12-dimethylbenz ［ a ］ anthracene (DMBA) and tumors in range of 2.19 ～ 3.81 cm 3 were applied to treatment experiment. Treatment condition was designed to reproduce the heat generation condition of the 1.36 cm 3 tumor treatment at every multiple injection site in rat mammary tumors. Tumor volume divided by number of injection sites (cm 3 / site) was set to close to 1.36 cm 3 / site and 45 mg MCL particles were administered at multiple sites to keep even spaces among injection sites. Three irradiation conditions were set to give close heat dose in vivo (J / cm 3 ) of the 1.36 cm 3 tumor treatment. Treatment under designed conditions resulted in complete regression of rat tumors at 21 days after the treatment, showing theoretical validity of design procedures for the multiple site injections. Novel concept of necrosed tumor volume from an injection site (cm 3 / site) and its actual value under a standard injection condition of 45 mg-MCL / site were described and its use in clinic was discussed.