Abstract

Purpose

The localized heating of magnetic nanoparticles (MNPs) via the application of time-varying magnetic fields – a process known as magnetic field hyperthermia (MFH) – can greatly enhance existing options for cancer treatment; but for broad clinical uptake its optimization, reproducibility and safety must be comprehensively proven. As part of this effort, the quantification of MNP heating – characterized by the specific loss power (SLP), measured in W/g, or by the intrinsic loss power (ILP), in Hm²/kg – is frequently reported. However, in SLP/ILP measurements to date, the apparatus, the analysis techniques and the field conditions used by different researchers have varied greatly, leading to questions as to the reproducibility of the measurements.

Materials and Methods

An interlaboratory study (across N = 21 European sites) of calorimetry measurements that constitutes a snapshot of the current state-of-the-art within the MFH community has been undertaken. Identical samples of two stable nanoparticle systems were distributed to all participating laboratories. Raw measurement data as well as the results of in-house analysis techniques were collected along with details of the measurement apparatus used. Raw measurement data was further reanalyzed by universal application of the corrected-slope method to examine relative influences of apparatus and results processing.

Results

The data show that although there is very good intralaboratory repeatability, the overall interlaboratory measurement accuracy is poor, with the consolidated ILP data having standard deviations on the mean of ca. ± 30% to ± 40%. There is a strong systematic component to the uncertainties, and a clear rank correlation between the measuring laboratory and the ILP. Both of these are indications of a current lack of normalization in this field. A number of possible sources of systematic uncertainties are identified, and means determined to alleviate or minimize them. However, no single dominant factor was identified, and significant work remains to ascertain and remove the remaining uncertainty sources.

Conclusion

We conclude that the study reveals a current lack of harmonization in MFH characterization of MNPs, and highlights the growing need for standardized, quantitative characterization techniques for this emerging medical technology.

中文翻译：

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磁热定性测量的挑战和建议

摘要

目的

通过应用随时间变化的磁场对磁性纳米颗粒（MNP）进行局部加热-一种称为磁场热疗（MFH）的过程-可以大大增强现有的癌症治疗选择；但是要获得广泛的临床应用，其优化，可重复性和安全性必须得到全面证明。作为这项工作的一部分，经常报告MNP加热的定量化-以比损耗功率（SLP）为单位，单位为W / g，或者以固有损耗功率（ILP）为单位，以Hm ² / kg为单位。但是，在SLP / ILP中 迄今为止的测量，不同研究人员使用的仪器，分析技术和现场条件相差很大，导致人们对测量的可重复性提出了质疑。

材料和方法

进行了一项 量热测量的实验室间研究（横跨N = 21个欧洲站点），该研究构成了MFH社区当前最新技术的快照。将两个稳定的纳米粒子系统的相同样品分配给所有参与的实验室。原始测量数据以及内部分析技术的结果与所用测量设备的详细信息一起被收集。通过普遍应用校正斜率方法进一步重新分析原始测量数据，以检查设备和结果处理的相对影响。

结果

数据显示，尽管实验室内的重复性非常好，但实验室间的整体测量精度却很差，合并后的ILP数据的平均值为ca的标准差。±30％至±40％。不确定性有很强的系统性成分，并且测量实验室和ILP之间存在明确的等级相关性。这些都表明该领域当前缺乏标准化。确定了系统不确定性的许多可能来源，并确定了减轻或最小化这些不确定性的手段。但是，没有一个单一的主导因素被确定，确定和消除剩余的不确定性来源仍需进行大量工作。

结论

我们得出的结论是，该研究揭示了MNP的MFH表征目前缺乏统一性，并强调了对这种新兴医学技术对标准化，定量表征技术的日益增长的需求。