Optimization and experimental characterization of the innovative thermo-brachytherapy seed for prostate cancer treatment.

ABSTRACT

BACKGROUND: Adjuvant administration of hyperthermia (HT) with radiation therapy in the treatment of cancer has been extensively studied in the past five decades. Concurrent use of the two modalities leads to both complementary and synergetic enhancements in tumor management, but presents a practical challenge. Their simultaneous administration using the same implantable thermo-brachytherapy (TB) seed source has been established theoretically through magnetically mediated heat induction with ferromagnetic materials. Careful consideration, however, showed that regular ferromagnetic alloys lack the required conductivity to generate enough power through eddy current to overcome heat dissipation due to blood perfusion at clinically measured rates. PURPOSE: We characterized the TB implant that combines a sealed radioactive source with a ferrimagnetic ceramic (ferrite) core, serving as a self-regulating HT source when placed in an alternating electromagnetic field. To increase the heat production and uniformity of temperature distribution the empty spacers between radioisotope seeds were replaced by hyperthermia-only (HT-only) seeds. METHODS: The heat generation due to eddy currents circulating in the seed's thin metal shell, surrounding the core, depends drastically on the core permeability. We identified a soft ferrite material ( MnZnFe 2 O 4 $\rm MnZnFe_2O_4$ ) as the best candidate for the core, owing to its high permeability, the HT-range Curie temperature, adjustable through material composition, and a sharp Curie transition, leading to heat self-regulation, with no invasive thermometry required. The core permeability as a function of temperature was calculated based on measured resistor-inductor (RL) circuit parameters and material B-H curves. The thickness of the shell was optimized separately for TB and HT-only seeds, having slightly different dimensions. Heat generation was calculated using the power versus temperature approximation. Finally, the temperature distribution for a realistic prostate LDR brachytherapy plan was modeled with COMSOL Multiphysics for a set of blood perfusion rates found in the literature. RESULTS: The small size of the investigated ferrite core samples resulted in demagnetization significantly decreasing the relative permeability from its intrinsic value of ∼5000 to about 11 in the range of magnetic field amplitude and frequency values relevant to HT. The power generated by the seed dropped sharply as the shell thickness deviated from the optimal value. The optimized TB and HT-only seeds generated 45 and 267 mW power, respectively, providing a HT source sufficient for >90% volume coverage even for the highest blood perfusion rates. The toxicity of the surrounding normal tissues was minimal due to the rapid temperature fall off within a few millimeters distance from a seed. CONCLUSIONS: The investigated TB and HT-only seed prototypes were shown to provide sufficient power for the concurrent administration of radiation and HT. In addition to being used as a source for both radiation and heat at the onset of cancer therapy, these implanted seeds would be available for treatment intensification in the setting of salvage brachytherapy for locally radiorecurrent disease, possibly as a sensitizer to systemic therapies or as a modulator of the immune response, without another invasive procedure. Experimentally determined parameters of the ferrite material cores provided in this study establish a mechanistic foundation for future pre-clinical and clinical validation studies.