Wust Peter, Gneveckow Uwe, Johannsen Manfred, Böhmer Dirk, Henkel Thomas, Kahmann Frank, Sehouli Jalid, Felix Roland, Ricke Jens, Jordan Andreas
Clinic for Radiotherapy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Int J Hyperthermia. 2006 Dec;22(8):673-85. doi: 10.1080/02656730601106037.
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.
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.
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 degrees C heat-coverage of 86%. However, the coverage with > or =42 degrees C is unsatisfactory at present (30% of the target volume in group A and only 0.2% in group B).
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 degrees C coverage towards 100% (98%). This illustrates the great potential of the nanofluid-based heating technology.
在全身磁场施加器MFH 300F和磁流体MFL 082AS研发出来之后，对磁流体热疗的概念进行了临床评估。这种用于局部热疗的新系统适用于热疗或热消融。由分散在水中的氧化铁纳米颗粒组成的磁流体必须分布在肿瘤中，随后通过在施加器中暴露于交变磁场来加热。我们对22例患有不同肿瘤实体的经过大量预处理的复发患者进行了一项可行性研究，在这些患者中，热疗联合放疗和/或化疗是一种选择。根据植入技术评估了（通过植入后分析）估计以及（通过改进技术）实现令人满意的温度分布的潜力。
建立了三种植入方法：CT透视引导下浸润（A组）、经直肠超声（TRUS）引导下X线透视植入（B组）和术中直视下浸润（C组）。在A组和B组中，可以在植入前根据三维图像数据集规划纳米颗粒的分布。比吸收率（SAR，单位为W/kg）可以从通过CT成像的颗粒分布以及实际的H场强度（单位为kA/m）得出。使用生物热传递方程计算肿瘤区域的温度分布，该方程评估一个平均灌注值，该值通过将计算出的温度与目标区域内或附近参考点的直接（侵入性或腔内）温度测量值相匹配来确定。
磁流体的滴注和热疗治疗分别耐受良好，无副作用或仅有中度副作用。在骨盆中使用3.0 - 6.0 kA/m的可耐受H场强度，在胸部和颈部区域高达7.5 kA/m，在头部大于10.0 kA/m，我们在目标区域实现了60 - 380 W/kg的SAR，导致40℃的热覆盖范围达到86%。然而，目前≥42℃的覆盖范围并不理想（A组为目标体积的30%，B组仅为0.2%）。
需要通过改进植入技术，或者仅仅通过增加纳米流体的量或提高磁场强度来进一步改善温度分布。从实际的纳米颗粒分布和得出的温度我们可以推断，仅将H场强度适度提高2 kA/m就会显著将42℃的覆盖范围提高到100%（98%）。这说明了基于纳米流体的加热技术的巨大潜力。
