Magnetic nanoparticles for interstitial thermotherapy – feasibility, tolerance and achieved temperatures
Background: The concept of magnetic fluid hyperthermia is clinically evaluated after development of the whole body magnetic field applicator MFH® 300F and the magnetofluid MFL 082AS. This new system for localized thermotherapy is suitable either for hyperthermia or thermoablation. The magnetic fluid, composed of iron oxide nanoparticles dispersed in water, must be distributed in the tumour and is subsequently heated by exposing to an alternating magnetic field in the applicator. We performed a feasibility study with 22 patients suffering from heavily pretreated recurrences of different tumour entities, where hyperthermia in conjunction with irradiation and/or chemotherapy was an option. The potential to estimate (by post-implantation analyses) and to achieve (by improving the technique) a satisfactory temperature distribution was evaluated in dependency on the implantation technique. Material and methods: Three implantation methods were established: Infiltration under CT fluoroscopy (group A), TRUS (transrectal ultrasound) – guided implantation with X-fluoroscopy (group B) and intra-operative infiltration under visual control (group C). In group A and B the distribution of the nanoparticles can be planned prior to implantation on the basis of three-dimensional image datasets. The specific absorption rates (SAR in W/kg) can be derived from the particle distribution imaged via CT together with the actual H-field strength (in kA/m). The temperature distribution in the tumour region is calculated using the bioheat-transfer equation assessing a mean perfusion value, which is determined by matching calculated temperatures to direct (invasive or endoluminal) temperature measurements in reference points in or near the target region. Results: Instillation of the magnetic fluid and the thermotherapy treatments were tolerated without or with only moderate side effects, respectively. Using tolerable H-field-strengths of 3.0–6.0 kA/m in the pelvis, up to 7.5 kA/m in the thoracic and neck region and >10.0 kA/m for the head, we achieved SAR of 60–380 W/kg in the target leading to a 40°C heat-coverage of 86%. However, the coverage with ≥42°C is unsatisfactory at present (30% of the target volume in group A and only 0.2% in group B). Conclusion: Further improvement of the temperature distribution is required by refining the implantation techniques or simply by increasing the amount of nanofluid or elevation of the magnetic field strength. From the actual nanoparticle distribution and derived temperatures we can extrapolate, that already a moderate increase of the H-field by only 2 kA/m would significantly improve the 42°C coverage towards 100% (98%). This illustrates the great potential of the nanofluid-based heating technology.
Description and characterization of the novel hyperthermia- and thermoablation-system MFH 300F for clinical magnetic fluid hyperthermia.
Magnetic fluid hyperthermia (MFH) is a new approach to deposit heat power in deep tissues by overcoming limitations of conventional heat treatments. After infiltration of the target tissue with nanosized magnetic particles, the power of an alternating magnetic field is transformed into heat. The combination of the 100 kHz magnetic field applicator MFH 300F and the magnetofluid (MF), which both are designed for medical use, is investigated with respect to its dosage recommendations and clinical applicability. We found a magnetic field strength of up to 18 kA/m in a cylindrical treatment area of 20 cm diameter and aperture height up to 300 mm. The specific absorption rate (SAR) can be controlled directly by the magnetic field strength during the treatment. The relationship between magnetic field strength and the iron normalized SAR (SAR(Fe)) is only slightly depending on the concentration of the MF and can be used for planning the target SAR. The achievable energy absorption rates of the MF distributed in the tissue is sufficient for either hyperthermia or thermoablation. The fluid has a visible contrast in therapeutic concentrations on a CT scanner and can be detected down to 0.01 g/l Fe in the MRI. The system has proved its capability and practicability for heat treatment in deep regions of the human body.
Non-contact actuation of triple-shape effect in multiphase polymer network nanocomposites in alternating magnetic field
Triple-shape polymers (TSP) can memorize two independent shapes, which are recovered when the temperature is subsequently increased. Certain applications do not allow triggering of the triple-shape effect (TSE) by environmental heating (e.g. potential damaging of surrounding tissue) and therefore require a non-contact activation. Here we explored whether polymer nanocomposites can be designed, which enable non-contact activation of TSE in an alternating magnetic field. A series of nanocomposites were synthesized by incorporation of silica coated iron(III)oxide nanoparticles into a polymer network matrix containing poly(e-caprolactone) (PCL) and poly(cyclohexyl methacrylate) (PCHMA) segments. Triple-shape functionalization of the materials was realized by application of different thermomechanical procedures (single or two dual-step), in which samples were deformed by bending to minimize changes in S/V ratio during shape recovery. For quantification of triple-shape properties inductive heating experiments were conducted in an alternating magnetic field at frequency of f = 258 kHz. By increasing the magnetic field strength H the triple-shape effect was triggered, while the maximum achievable temperature Tmax and the shape change was monitored using an infrared video camera. Excellent triple-shape properties were achieved for nanocomposites containing 40 wt-% of PCL exhibiting a two-step recovery of shapes B and C, when stimulated by step-wise increasing the magnetic field strength. In this way the TSE could be characterized by two distinct switching magnetic strengths Hsw,1(A → B) and Hsw,2(B → C) corresponding to the switching temperatures determined in cyclic, thermomechanical tensile tests for thermally-induced TSP.
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