Joseph A. Paulus

Evaluation of inductively heated ferromagnetic alloy implants for therapeutic interstitial hyperthermia

Ferromagnetic alloys heated by magnetic induction have been investigated as interstitial hyperthermia delivery implants for over a decade, utilizing low Curie temperatures to provide thermal self-regulation. The minimally invasive method is attractive for fractionated thermal treatment of tumors which are not easily heated by focused microwave or ultrasound techniques. Past analyses of ferromagnetic seeds by other authors depict poor experimental correlation with theoretical heating predictions. Improvements in computer hardware and commercially available finite element analysis software have simplified the analysis of inductively heated thermal seeds considerably. This manuscript examines end effects of finite length implants and nonlinear magnetic material properties to account for previous inconsistencies. Two alloys, Ni-28 wt% Cu (NiCu) and Pd-6.15 wt% Co (PdCo), were used for comparison of theoretical and experimental calorimetric results. Length to diameter (L/d) ratios of over 20 for cylindrical seeds are necessary for minimization of end effects. Magnetic properties tested for alloys of NiCu and PdCo illustrate considerable nonlinearity of these materials in field strength ranges used for induction heating. Field strength dependent magnetic permeabilities and calorimetric data illustrate that more detailed material information must be included to accurately estimate induction power loss for these implants.

Corrosion analysis of NiCu and PdCo thermal seed alloys used as interstitial hyperthermia implants

Ferromagnetic materials with low Curie temperatures are being investigated for use as interstitial implants for fractionated hyperthermia treatment of prostatic disease. Previous investigations of the system have utilized alloys, such as NiCu, with inadequate corrosion resistance, requiring the use of catheters for removal of the implants following treatment or inert surface coatings which may interfere with thermal characteristics of the implants. We are evaluating a palladium-cobalt (PdCo) binary alloy which is very similar to high palladium alloys used in dentistry. Electrochemical corrosion tests and immersion tests at 37 degrees C for both NiCu and PdCo alloy samples in mammalian Ringers solution were performed. Long-term corrosion rates are 5.8 x 10(-5) microm per year (NiCu) and 7.7 x 10(-8) microm per year (PdCo) from average immersion test results, indicating higher corrosion resistance of PdCo (P < 0.02); immersion corrosion rates were much lower than initial corrosion rates found electrochemically. Both alloys had significantly lower corrosion rates than standard surgical implant rates of 0.04 microm per year (P < 0.001 for both alloys). Scanning electron microscopy illustrates changes in the NiCu alloy surface due to pitting corrosion; no difference is observed for PdCo. The data indicate that the PdCo alloy may be suitable as a long-term implant for use in fractionated hyperthermia.

The Effect of Interstitial Hyperthermia on the Dunning Prostate Tumor Model

The effect of hyperthermia was examined on the Dunning prostate tumor model in rats. Hyperthermia was created by heating self-regulating interstitial seeds with an external oscillating magnetic field. The seed alloy was comprised of 70% nickel and 30% copper. One treatment with 50C seeds for two hours did not provide significant delay in tumor growth compared to controls. However, regimens with two treatments separated by either 48 hours or one week did cause significant delay (p = 0.0013 and p = 0.0096, respectively). These results suggest that an interstitial hyperthermia seed may provide an efficacious outpatient therapy for prostate cancer. Further, interstitial hyperthermia may be readily combined with existing radiotherapy with interstitial gold coated seeds to provide additive or synergistic anti-tumor effects.

HSP 70 induction and thermotolerance following interstitial hyperthermia in the dunning R3327 tumor in vivo

We investigated the use of an interstitial temperature self-regulating implant for fractionated hyperthermia delivery for treatment of prostatic disease. Nonuniform heating, lower temperatures between the implants, and lingering thermotolerance for additional hyperthermia treatments are concerns associated with the technique. Thermotolerance of the Dunning R3327 prostate adenocarcinoma to a 1 hour interstitial heating of 42-43°C has been estimated using inducible heat shock protein (HSP) 72 as an assay. The duration of thermotolerance in a nonuniformly heated tumor is necessary for optimization of multiple-treatment planning. HSP 72 expression is increased between 8 and 16 hours posttreatment. Growth curves for conditioned (treated once at 42-43°C minimum) tumors retreated at a minimum temperature of 45°C after 10 hours recovery (where elevated HSP 72 expression is evident) were compared with those retreated after 48 hours recovery (with normal HSP 72 expression) and with conditioned controls; both retreatment groups differed from controls (p < 0.0001). Growth curves for tumors with elevated HSP 72 expression after 10 hours differed from those retreated after 48 hours (p ≤ 0.0202). The results indicate that in vivo measurement of HSP 72 expression in the Dunning tumor is an adequate indicator of thermotolerance for optimal sequencing of hyperthermia fractions and that sufficiently high thermal doses are effective against thermotolerant cell populations.