Institute of Diagnostic and Interventional Radiology, Department of Experimental Radiology, Jena University Hospital - Friedrich Schiller University Jena, Jena, Germany.
Resonant Circuits Limited, London, UK.
Int J Hyperthermia. 2021;38(1):743-754. doi: 10.1080/02656736.2021.1912412.
Deep-tissue localization of thermal doses is a long-standing challenge in magnetic field hyperthermia (MFH), and remains a limitation of the clinical application of MFH to date. Here, we show that pulse sequencing of MFH leads to a more persistent inhibition of tumor growth and less systemic impact than continuous MFH, even when delivering the same thermal dose.
We used an orthotopic murine model of pancreatic PANC-1 cancer, which was designed with a view to the forthcoming 'NoCanTher' clinical study, and featured MFH alongside systemic chemotherapy (SyC: gemcitabine and nab-paclitaxel). In parallel, thermal modelling was implemented.
Tumor volumes 27 days after the start of MFH/SyC treatment were 53% (of the initial volume) in the pulse MFH group, compared to 136% in the continuous MFH group, and 337% in the non-treated controls. Systemically, pulse MFH led to ca. 50% less core-temperature increase in the mice for a given injected dose of magnetic heating agent, and inflicted lower levels of the stress marker, as seen in the blood-borne neutrophil-to-lymphocyte ratio (1.7, compared to 3.2 for continuous MFH + SyC, and 1.2 for controls).
Our data provided insights into the influence of pulse sequencing on the observed biological outcomes, and validated the nature of the improved thermal dose localization, alongside significant lowering of the overall energy expenditure entailed in the treatment.
在磁场热疗（MFH）中，深层组织热剂量定位是一个长期存在的挑战，这也是迄今为止 MFH 临床应用的一个局限性。在这里，我们表明，与连续 MFH 相比，MFH 的脉冲序列会导致肿瘤生长的持续抑制和较少的全身影响，即使给予相同的热剂量。
我们使用了一种原位胰腺 PANC-1 癌的小鼠模型，该模型是为即将进行的“无癌治疗”临床研究而设计的，其特点是 MFH 联合全身化疗（SyC：吉西他滨和 nab-紫杉醇）。同时，还进行了热建模。
在 MFH/SyC 治疗开始后 27 天，脉冲 MFH 组的肿瘤体积为初始体积的 53%，而连续 MFH 组为 136%，未治疗对照组为 337%。在全身范围内，与连续 MFH+SyC 相比，脉冲 MFH 导致接受相同注射剂量磁加热剂的小鼠核心温度升高减少约 50%，并且血液中中性粒细胞与淋巴细胞比值（1.7）降低，而连续 MFH+SyC 为 3.2，对照组为 1.2。
我们的数据提供了关于脉冲序列对观察到的生物学结果的影响的见解，并验证了改进的热剂量定位的性质，同时还显著降低了治疗所需的总能量消耗。
