No abstract

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.

Ferromagnetic Ni-Cu alloy wires were characterized in order to obtain well-defined thermoseeds for application in interstitial hyperthermia of prostate cancer. Thermoseeds have been produced which possess Curie points in the therapeutic hyperthermia range, approximately 40 to 50 degrees C. The effect of thermal treatment and composition on the heating characteristics of the thermoseeds were investigated. The preliminary study shows that the recrystallization is crucial for altering thermoseeds' heating characteristics. Obtaining thermoseeds which behave as desired depends on changes in annealing times and temperatures. One may increase the maximum heating temperature (similar to Curie temperature) by increasing the annealing time and cooling time. Decreasing the lower annealing plateau temperature also increases the maximum seed heating temperature. Higher nickel content compositions did not affect rise time but increased the maximum heating temperature.

Hyperthermia is being utilized individually and in conjunction with other therapies in treating malignant and benign tumors, though few studies have examined cellular effects of elevated temperatures in the prostate model. Highly conserved proteins of the 70 kDa heat shock protein family (HSP 70) are produced in response to environmental stresses, including heat, and are found in all organisms. HSPs are an indicator of cell damage, are associated with thermotolerance, and provide cells with transient resistance to subsequent thermal challenges. Transient thermotolerance is important in the determination of temperature, duration, and sequencing for treatments. This preliminary study analyzes the HSP 70 response of the Dunning R3327 adenocarcinoma model to a single 50 degrees C 1 hr treatment. Elevated HSP levels were found between 10 and 16 hr, returning to baseline by 24 hr. As some fractions of the cells are able to produce HSP 70 following treatment, the data suggest that currently utilized clinical temperatures (42-46 degrees C) administered for 1 hr are inadequate. HSP levels in response to hyperthermia, radiation, and chemotherapy may be useful in finding optimal treatment regimens for prostate cancer.

An interstitial temperature self-regulating implantable thermal seed for ablation of the prostate was investigated for the treatment of cancer. The technique is analogous to brachytherapy implants with three important advantages: highly localized temperatures may reduce complications, the thermal seed can be activated for retreatment at any point in time, and the seeds pose no radiation hazard to the clinical staff. Thermal seeds were implanted in the left lobe of the prostates in four dogs; the right lobe was a control to evaluate undesired heating outside the seed array. Linear-array thermometry probes were placed in both lobes, and the induction field for heating the implants was activated for 1 hour. After treatment, biopsies were taken from both lobes at 4-hour intervals up to 28 hours to evaluate thermal damage and thermotolerance as measured by expression of heat shock protein (hsp) 70. Only 5 minutes was required to heat the left lobe to 45 degrees to 55 degrees C. The maximum and minimum cumulative equivalent minutes at 43 degrees C (CEM43) thermal doses in the treated lobe were 174 and 4.4 hours, respectively; less than a 1-minute CEM43 was observed in the control lobe. Elevated hsp70 expression was detected in tissue of the treated lobe between 12 and 24 hours after treatment; minimal increases occurred in the control lobe. The thermal seed system was effective at heating the prostatic volume without damage to normal tissues outside the implant array, and subsequent treatments were simplified in comparison with other hyperthermia devices. Expression of hsp70 implies that retreatment of the prostate at intervals as short as 48 to 72 hours may avoid thermotolerance making weekly treatment an appropriate regimen.