Heat Dose Index in vivo for Cancer Therapy Using Heat-generating Nanoparticles Named Magnetite Cationic Liposomes and Alternating Magnetic Field Irradiator

Abstract

Cancer clinical research using heat-generating nanoparticles named magnetite cationic liposomes (MCL) and alternating magnetic field (AMF) irradiator has been conducted. Heat generation from intratumorally injected MCL particles was triggered by AMF irradiation to kill cancer cells nearby located. Tumor temperature was monitored as index to control treatment condition but efficacy was variable from complete regression to ineffective. In order to improve efficacy, we have proposed novel index of heat dose in vivo (J/cm3 tumor volume). Purpose of this study was to reveal actual heat dose in vivo and discuss its utility as index. In order to enable to estimate heat dose, heat generation activity of MCL particles (J/g-MCL・min) was measured under various AMF irradiation conditions by changing output power (kW) and distance from irradiation surface (mm). Treatment condition for complete regression of animal tumors with 7 mm diameter was reproduced and heat dose in vivo (J/cm3) was calculated by multiplying heat generation activity (J/gMCL・min) with MCL dosage (g-MCL/cm3) and irradiation time (min). Heat dose for tumor regression was revealed around 700-850 J/cm3 in every thrice AMF irradiations of a course. Since temperature-based treatments of large tumors were reported to fall into insufficiency, revealed heat dose was applied to design treatment condition of large tumor with 13-16 mm diameter, and complete regression was achieved by a course treatment. MCL dosage of temperature-based condition was found far lower than that of heat dose. Low MCL dosages (g-MCL/cm3) would cause shortage of heat dose (J/cm3) and insufficient anticancer activity, although tumor temperature could be raised by heat transfer to monitoring sites. These results showed utility of heat dose in vivo as index to ensure clinical efficacy and concomitantly to make useless invasive probe for temperature monitoring. Procedure to design treatment condition and required performance of AMF irradiator Heat dose in vivo of nanoparticles ・ T. Morino et al. 47 ― ― Received: 15 April, 2020, Accepted: 17 June, 2020: *Correspondence author; Tel, +81-52-853-8266; Fax, +81-52-852-3179; e-mail; t-morino@med.nagoya-cu.ac.jp doi: 10.3191/thermalmed.36.47 ©2020 Japanese Society for Thermal Medicine