Effects of Magnetic Fluid Hyperthermia (MFH) on C3H mammary carcinomain vivo

Abstract

Magnetic fluids (MF) have a potential for hyperthermia due to their good power absorption capabilities. Recent in vitro experiments with the so-called 'Magnetic Fluid Hyperthermia (MFH)' have shown that human tumours cells are homogeneously inactivated after AC magnetic field excitation of extracellular MF. The aim of the present study was the evaluation of a high dose MFH on intramuscularly implanted mammary carcinoma of the mouse. The tumours originated from initial in vivo passages of a spontaneous parent tumour. Because of larger variations of tumour growth in this rather primary model, logistic regression of non-averaged volumes was performed for each treatment modality. All growing tumours were randomized 30 days after transplantation (day of treatment) with an overall size distribution between 120-400 mm3. An intratumoural steady state temperature of 47 +/- 1.0 degrees C was maintained for 30 minutes with whole-body AC magnetic fields of 6-12.5 kA/m at 520 kHz. The magnetic fluid was #P6, which is a high biocompatible dextran magnetite. #P6 was given intratumourally (1.5 x 10(-2) mg ferrite/mm3) 20-30 minutes before excitation and was combined with magnetic targeting (50 mT), which yielded a 2.5-fold enhancement of the intratumoural iron concentration. Histological examinations of tumour tissue after intralesional ferrofluid administration alone indicated deep infiltration of the fluid into the carcinoma tissue, but no evidence of tissue damage as compared with untreated controls. In contrast, widespread tumour necrosis was observed after MFH. After application of either dextran or ferrofluid alone (no difference, p = 0.665), tumour growth was slightly delayed in comparison with untreated controls (p < 0.001). In contrast to the good fit of the controls (R = 0.92-0.87), tumour growth after MFH was much more heterogeneous; some tumours showed no evidence for regrowth at 50 days whereas others had grown quite readily. This most probably reflected the critical problem of homogeneity of the intratumoural MF distribution, which was also confirmed qualitatively by Magnetic Resonance Imaging (MRI), heterogeneous pigmentation of MFH treated tumours, and up to 1 degree C differences between temperature probes in the same tumour during AC magnetic field application. However, a quantitative comparison between intratumoural MF-heterogeneity and tumour response could not be performed in this study. Despite these current limitations, the regression analysis of the MFH data yielded a smaller tumour volume of about 1000 mm3 at 50 days growth time in contrast to all three controls. In conclusion, encouraging results have been obtained, which show, that one single high dose MFH is already able to induce local tumour control in many cases within 30 days after treatment. To overcome the uncertainties of intratumoural MF heterogeneity, advanced intralesional application methods are currently under development.

Maghemite Functionalization for Antitumor Drug Vehiculization

“…Numerous studies have proved the efficacy of this therapy in animal models (Moroz et al, 2002) and there have been presented reports of the satisfactory application of this method in investigations on cells and human tissues (Chan et al, 1993;Jordan et al, 1996Jordan et al, , 1997. As a result, hyperthermia has been accepted by the FDA to utilize it alone or in combination with radiation in cases of some solid malignant tumors which are present onto and under the surface of the body (e.g.…”

Clinical applications of magnetic nanoparticles for hyperthermia

“…Injection of micro-scaled ferromagnetic particles into renal carcinomas of rabbits and subsequent heating was reported by Rand et al in 1981 [9]. Direct injection of dextran-coated magnetite nanoparticles with a core size of approximately 3 nm into tumors was first reported by our group in 1997 [10]. Hilger et al injected colloidal suspensions of coated nanoparticles (particle sizes of 10 nm and 200 nm) into human carcinomas implanted into mice and described 'magnetic thermal ablation' [11].…”

Field dependent transition to the non-linear regime in magnetic hyperthermia experiments: Comparison between maghemite, copper, zinc, nickel and cobalt ferrite nanoparticles of similar sizes

“…In addition, several other novel potential applications have been proposed over the past few decades concerning, in particular, cancer treatment through the delivery of drugs, genes, peptides or heat. [8][9][10][11][12][13][14][15][16][17] The heating of tumorous cells is based upon the magnetic hyperthermia phenomenon, which consists of an increase in the temperature of magnetic nanoparticles due to the interaction of their magnetic moments with an alternating magnetic field. Recently, there has been a considerable effort from the community to develop more efficient heating centers.…”