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.
Highlights
Cancer remains a leading public health challenge facing humanity in the twenty first century
The goal of the study was to determine the reproducibility of specific loss power (SLP) and/or intrinsic loss power (ILP) measurements acquired at different participating laboratories using a universal measurement protocol, and the same magnetic nanoparticles (MNPs) preparations
Subsequent single-operator Corrected Slope Method [15] (CSM) reanalysis confirmed this agreement, with the intra-laboratory standard deviation in the three consecutive measurements generally being of order ±2% to ±6%
Summary
Cancer remains a leading public health challenge facing humanity in the twenty first century. The most established methods of cancer treatment at present are surgery, radiotherapy and chemotherapy. These techniques have shown significant progress in recent decades, and are complemented today by other more recently developed techniques such as immunotherapy [2] or hormonotherapy [3]. There remains a significant need for innovative approaches which improve patient outcomes, while minimizing the trauma and collateral damage associated with established cancer therapies. Magnetic field hyperthermia (MFH), referred to as magnetic fluid hyperthermia, is an emerging technique capable of complementing or replacing established cancer therapies [4,5].
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