Challenges and recommendations for magnetic hyperthermia characterization measurements

Abstract

Purpose: The localized heating of magnetic nanoparticles (MNPs) via the application of time-varying magnetic fieldsa 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 heatingcharacterized by the specific loss power (SLP), measured in W/g, or by the intrinsic loss power (ILP), in Hm 2 /kgis 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.

Understanding MNPs Behaviour in Response to AMF in Biological Milieus and the Effects at the Cellular Level: Implications for a Rational Design That Drives Magnetic Hyperthermia Therapy toward Clinical Implementation

“…One of the main limitations for the critical analysis of MHT measurements is how to determine the heating power of MNPs [ 71 ]. The Specific Absorption Rate (SAR) is an empirical parameter frequently used by radiological protection departments to regulate the amount of radiation absorbed by patients when exposed to radiofrequency fields and it is normalized to the mass of biological tissue irradiated in terms of W/g [ 72 ].…”

“…This model predicts a linear dependence of the SAR on the frequency and a quadratic dependence on H, although this is only valid for highly anisotropic MNPs and a small H, and thus, it cannot be assumed as a universal parameter. Besides, recent double-blind experiments showed that the specific features of the experimental set-ups and the thermal curves analysed may produce inconsistent SAR values between laboratories [ 71 ]. A promising solution to achieve a global and consistent parameter to determine heating power is to measure the high frequency magnetic loop of the MNPs [ 76 ].…”

Time-dependent AC magnetometry and chain formation in magnetite: the influence of particle size, initial temperature and the shortening of the relaxation time by the applied field

“…The magnetic fluid hyperthermia is a well-known method that takes advantage of the heat released by magnetic nanoparticles when subjected to radiofrequency fields; the heat released leads to cancer cell apoptosis or necrosis and, consequently, it is an appropriate method for the treatment of tumours 1 . The deep comprehension of the influence of the nanoparticle properties, colloidal media as well as the frequency and amplitude field range is relevant to optimizing the conditions for future successful clinical applications [2][3][4] . Ac-calorimetry is the most common technique for the characterization of the heating efficiency; however, the most recent ac magnetometry methods 5,6 has been proven to be a very useful tool to obtain valuable information about the magnetic properties of the dynamic systems, which is not accessible from the calorimetric measurements.…”

Reproducibility and Scalability of Magnetic Nanoheater Synthesis

“…In general, the effect of the nanoparticle size on the heating capacity of a suspension of MNPs under an alternating magnetic field is expected to increase as particle size increases, although many other factors can mask this result due to collective behavior forming chains, for example, and poor colloidal stability, which can lead to huge errors due to the precipitation of nanoparticles ( Figure S2 ). Such sample degradation issues complicate the comparison between different MNPs and equipment [ 26 ]; however, experimental data in the literature have shown SAR values between 20 and 65 W/g (40 kAm −1 , 77 kHz) for samples synthesized by thermal decomposition in 1-octadecene, with the same mean size (14 nm) but different size distribution [ 27 ]. The highest SAR was closer to the data reported here under similar field conditions and was associated with the sample with the narrowest size distribution.…”