Hyperthermia of pet animal tumours with self-regulating ferromagnetic thermoseeds

Abstract

Investigations with thermally self-regulating ferromagnetic implants (thermoseeds) were done on healthy rats and pet animals with spontaneous and transmissible venereal tumours (TVT). The thermoseeds were produced from a nickel-copper alloy and electroplated with a gold-silver layer. Manufacturing conditions were varied to produce thermoseeds with various operating temperatures, the critical temperature above which heating power production sharply declines. To test for toxicity, thermoseeds were implanted into the liver of rats and left in place for up to 14 months. While atomic absorption spectroscopy showed increased nickel and copper levels in tissues near the implants, no clinical evidence of ill-effects was noted. For hyperthermia treatment, diermoseeds were implanted into tumours of pet animals, and these were placed into an induction coil which produced an 89 kHz frequency, 4000 A/m amplitude field. The highest recorded tumour temperature correlated with the nominal operating point of the thermoseeds, demonstrating their ability to regulate the temperature. Of the 15 evaluable animals with spontaneous tumours treated, 12 received concomitant ⁶⁰Co radiation (two of them only after tumour recurrence following an initial treatment course of hyperthermia alone). Five of those treated with both modalities experienced complete response, five responded partially and two had no change. The treatment course of hyperthermia alone resulted in one animal achieving a complete response, and in three partial responders. Animals bearing TVT had a complete local response with hyperthermia alone. Massive tissue necrosis and seed migration caused the major treatment-related toxicity. Our findings suggest that self-regulating thermoseeds offer the possibility of predictable heat delivery to defined tissue volumes, and may be useful in the treatment of human tumours which are amenable to implantation. Until migration can be controlled, clinical trials should be limited to removable implants.