EFFECTS OF MAGNETIC FLUID HYPERTHERMIA (MFH) ON C3H MAMMARY-CARCINOMAIN-VIVO

Magnetic fluids (MF) have a potential for hyperthermia due to their go od power absorption capabilities. Recent in vitro experiments with the so-called 'Magnetic Fluid Hyperthermia (MFH)' have shown that human t umour cells are homogeneously inactivated after AC magnetic field exci tation of extracellular MF. The aim of the present study was the evalu ation of a high dose MFH on intramuscularly implanted mammary carcinom a of the mouse. The tumours originated from initial in vivo passages o f a spontaneous parent tumour. Because of larger variations of tumour growth in this rather primary model, logistic regression of non-averag ed volumes was performed for each treatment modality. All growing tumo urs were randomized 30 days after transplantation (day of treatment) w ith an overall size distribution between 120-400 mm(3). An intratumour al 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 k Hz. The magnetic fluid was #P6, which is a high biocompatible dextran magnetite. #P6 was given intratumourally (1.5 x 10(-2) mg ferrite/mm(3 )) 20-30 minutes before excitation and was combined with magnetic targ eting (50 mT), which yielded a 2.5-fold enhancement of the intratumour al iron concentration. Histological examinations of tumour tissue afte r intralesional ferrofluid administration alone indicated deep infiltr ation of the fluid into the carcinoma tissue, but no evidence of tissu e damage as compared with untreated controls. In contrast, widespread tumour necrosis was observed after MFH. After application of either de xtran or ferrofluid alone (no difference, p = 0.665), tumour growth wa s 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 gr owth after MFH was much more heterogeneous; some tumours showed no evi dence for regrowth at 50 days whereas others had grown quite readily. This most probably reflected the critical problem of homogeneity of th e intratumoural MF distribution, which was also confirmed qualitativel y by Magnetic Resonance Imaging (MRI), heterogeneous pigmentation of M FH treated tumours, and up to 1 degrees C differences between temperat ure probes in the same tumour during AC magnetic field application. Ho wever, a quantitative comparison between intratumoural MF-heterogeneit y and tumour response could not be performed in this study. Despite th ese current limitations, the regression analysis of the MFH data yield ed a smaller tumour volume of about 1000 mm(3) 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 alrea dy able to induce local tumour control in many cases within 30 days af ter treatment. To overcome the uncertainties of intratumoural MF heter ogeneity, advanced intralesional application methods are currently und er development.