Feasibility Study Of Magnetic Fluid Hyperthermia Induced By Radiofrequency Capacitive Field With Low Output Power For Treating Transplanted Subcutaneous Tumor In Rats

Background:In recent years, radiofrequency-induced hyperthermia has increasingly attracted attention for the generation of heat in a desired zone, even in tumors deeply located inside a patient's body. The limitation of radiofrequency hyperthermia in clinical use include no tissue-specific heating because of indistinct border between heating area and no heating area, over-heating in fat tissues and require high output power(1000-2000 W). The desirable radiofrequency hyperthermia for tumor treatment has not been reached although a lot of endeavours through engineering principles and methods for overcoming these limitation have been done.Radiofrequency ablation is a commonly used technique for the treatment of localized tumors in liver, with increasing application in other organs such as kidney, bone, lung, adrenal gland and prostate. Local recurrence and survival rates depend on the rate of complete ablation of the entire tumour including a sufficient margin of surrounding healthy tissue. Although a variety of different RFA devices with radical cluster multielectrode that could increase ablation region are available currently, that only depenging on increasing ablation diameter could not be able to meet th need for tumor conformal therapy in clinically because the size and geometry of tumour offen are irregular. In order to complete ablate the entire tumour, the damage of radiofrequency ablation to healthy tissues and organs surrounding tumor was inevitable at present because the shape of tissue ablation necrosis generated by routine radiofrequency technology is offen regular.Magnetic fluid hyperthermia(MFH) has been becaming a new heating technology in the treatment of malignant tumors because of having a character of heating the tumor tissue precisely and properly and a significant therapetic effect.MFH for tumor therapy could improve regional control and decrease the risk of complications related to the over-heating in normal tissues hyperthermia.Literatures about MFH induced by radiofrequency capacitive field with low power for tumor treatment have not been reported.The purpose of this study is to investigate the heating effects of magnetic nanoparticles induced by radiofrequency capacitive field with low power and evaluate the feasibility of treating transplanted subcutaneous tumor model in Wistar rats.Part I Heating efficacy of namimiter magnetic fluid hyperthermia induced by radiofrequency capacitive field with low powerObjectives:This study aimed to evaluate the heating efficacy of magnetic nanoparticles induced by radiofrequency capacitive field(RCF) with low power.Methods:Fe3O4 magnetic fluid in centrifuge tube packed with polystyrene foam plastics in order to thermal insulation, was dealt with 27.1 MHz,150W radiofrequency field produced by Erbtherm 1100 P hyperthermia system. The temperature of magnetic fluids under 27.1 MHz radiofrequency field was detected by It-Cu-ConCu thermocouple thermometer and recorded dynamically by temperature-recording instrument with 4 channels, and contrasted with normal saline (NS) and distilled water (DW)Results:It was found that the temperature of Fe3O4 magnetic fluid (75-150 mg/mL) could be raised by radiofrequency field with 90-150 W, and obviously higher than that of NS and DW under the same conditions. The heating rates of the magnetic fluids were in direct linear proportion to the power of radiofrequency field and concentration of particles. Being dealt with 27.1 MHz.150W radiofrequency field for 30 min. the temperature of magnetic fluid could be raised to about 70.2℃and retained this level, whereas the temperature of NS and DW were remarkably lower than that of it.Conclusions:It is obvious that the effective temperature of Fe3O4 magnetic fluid induced by 27.1 MHz radiofrequency field for cancer hyperthermia can be obtained, the heating efficiency of Fe3O4 magnetic fluid under radiofrequency field was determined by the power of radiofrequency field, concentration of particles,dosage and acting time.Part II Heating efficacy of namimiter magnetic fluid induced by radiofrequency capacitive field with low powerObjectives:To assess the heating efficacy of nanometer magnetic fluid induced by radiofrequency capacitive field in normal rat muscle.Methods:32 normal rats were randomly divided into five groups, including MFH A, B, C and D group, all recepted RF radiation with the output power of 90 W,110 W,130 W and 150 W respectively after injection of magnetic fluid 1 mL 24h. The disired temperature(50℃) was maintained for 30mins by manually adjusting the output power. CT scanning was performed after injection, 1h,24h and after hyperthermia repectively. Blood routine and their function of liver and kidney of rats were tested before and after hyperthermia respectively.Results:Temperature of magnetic fluid in rats placed under a RF field rose rapidly. In 130 W,150 W, the core and rim temperature both rose rapidly and reached the desired temperature about 50℃within the first 10 to 15mins, and then was maintained in a relatively constant range of 50℃±2℃for 30mins by manually adjusting the output power. The limited highter density imaging of intramuscular magnetic fluid deposits compared to the surrounding tissue was observed clearly by CT scanning. No significant differences were found in serum AST, ALT, BUN,Cr levels and blood routine among the rats of all groups (P> 0.05).Conclusions:The nanometer magntic fluid induced by radiofrequency capacitive field with power of 90-150 W has good heating efficacy both in vitro and in vivo. The homogeneous high and relatively stable-state intramuscular temperature of 50℃can be obtained successfully. CT can be served as a sensitive method to detect the distribution of intramuscular magnetic fluid. Part III Establishment of Walker-256 transplanted subcutaneous tumours in wistar ratsObjectives:To establish transplanted subcutaneous tumour models of Walker-256 cancer cells in Wistar rats.Methods:Thirty Wistar rats were implanted Walker-256 cells into the subcutaneous tissue of the right thigh to estabilish Walker-256 transplanted subcutaneous tumours model. Eight, fourteen, twenty-one and twenty-eight days after tumor implantation, tumor diameter and size were monitored by a vernier caplier, ultrasongraphy and MRI examination respectively, and then they were compared with each other. The phathologic features of Walker-256 transplanted subcutaneous tumours were observed by HE staining.Results:The successful rate of the transplanted subcutaneous tumor model was about 95.56%(86/90 cases). The natural survival time of the subcutaneous tumor model in rats was about 32.15±1.26 days.Tumor size was similar with the same growth time, and there was no significant difference between each other(P>0.05). The maximum tumor diameters measured by ultrasound and MRI respectively had no significant difference (P>0.05). The nested distribution of transplanted subcutaneous tumor cells with multinuclear division was examined by HE staining.Conclusions:The Walker-256 transplanted subcutaneous tumours in model rats can be duplicated by highly successful rate. Ultrasonography and MRI are useful in measuring tumor size and monitoring its change,but power MRI is more sensitive to detecte small tumor, especially for distirbution of tumor edege by contrast ultrasongraphy.Part IV Feasibility study of magnetic fluid hyperthermia induced by radiofrequency capacitive field with low output power for treating transplanted subcutaneous tumor in ratsObjective To study the feasibility of magnetic fluid hyperthermia induced by radiofrequency capacitive field with low output power for treating transplanted subcutaneous tumor in Wistar rats and assess the effect of it on growth of tumor.Methods Fifty rats bearing subcutaneous tumor 8-9days after tumor implantation were randomly divided into five groups,including the pseudo-treatment(PT) control group, normal saline(NS) control group,magnetic fluid (MF) control group, magnetic fluid hyperthermia I (MFH1) group, magnetic fluid hyperthermia II (MFH2) group. After 24 hour the Fe3O4 magnetic fluid (MF) was locally injected in the tumor area, the rats were exposed to RF capacitive field and subsequently heated at 50℃for 30mins for group MFH1, and repeated hyperthermia with 72h interval for group MFH2. The parameters of the RF capacitive field were carefully adjusted until a local tumor temperature (50℃) was maintained for 30 min. CT scanning was performed at 1 day after 1st and 2nd hyperthermia respectively. The tumour volume, rate of tumor volume inhibition, rats survival time, serum cytokines IL-2 and IL-10 were examined.Results The temperature of core and rim tumor both rapidly and reached the desired temperature about 50℃within the first 5 to 10mins,and then was maintained in a relatively constant range of 50℃±2℃for 30mins by manually adjusting the output power. The limited higher density imaging of intratumoral magnetic fluid deposits compared to the surrounding tissue was observed clearly by CT scanning.MFH 1 or MFH2 could inhibit the tumor growth. Compared with MFH1, MFH2 had a greater inhibitive effect on tumor growth (P＜0.05). The inhibitive rates of tumor volume from 1st week to the 4th weekatMFH1 group and MFH2 group was 32.46%,50.62%,48.86%,39.35%and 40.82%,72.32%,74.41%,73.26% respectively. The survival time of MFH2 group and MFH1 group were more prolonged than that of control group (P＜0.05).When compared with the other groups, the expression of IL-10 was remarkably decreased and IL-2 was increased at MFH1 and MFH2 group, has significant difference between the two groups (P<0.05).Conclusion The results obtained indicated that mamietic fluid hyperthermia induced by radiofrequency capacitive field with low output power could generate homogeneous high and relatively stable-state intratumoral temperature of 50℃for tumor treatment in MFH1 and MFH2 group.The tumor of model rats in MFH2 group might be all disappear by this hyperthermia which showed more effective inhibition of tumor growth.