J Wells1, D Ortega2,3, U Steinhoff1, S Dutz4, E Garaio5, O Sandre6,7, E Natividad8, M M Cruz9, F Brero10, P Southern11,12, Q A Pankhurst11,12, S Spassov13. 1. Physikalisch-Technische Bundesanstalt, Berlin, Germany. 2. Condensed Matter Physics department, Faculty of Sciences, Campus Universitario Río San Pedro s/n, Cádiz, Spain. 3. IMDEA Nanociencia, Ciudad Universitaria de Cantoblanco, Madrid, Spain. 4. Technische Universität Ilmenau, Institut für Biomedizinische Technik und Informatik, Ilmenau, Germany. 5. Nafarroako Unibertsitate Publikoan, Pamplona, Spain. 6. Université de Bordeaux, Pessac, France. 7. CNRS, Laboratoire de Chimie des Polymères Organiques, Pessac, France. 8. Instituto de Nanociencia y Materiales de Aragón (INMA), CSIC-Universidad de Zaragoza, Zaragoza, Spain. 9. BioISI, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal. 10. Dipartimento di Fisica, Università degli studi di Pavia, Pavia, Italy. 11. Healthcare Biomagnetics Laboratory, University College London, London, UK. 12. Resonant Circuits Limited, London, UK. 13. Centre de Physique du Globe de l'Institut Royal Météorologique, Dourbes, Belgium.
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.
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.
Authors: Liliana P Ferreira; César P Reis; Tiago T Robalo; M E Melo Jorge; Paula Ferreira; Joana Gonçalves; Abdollah Hajalilou; Maria Margarida Cruz Journal: Nanomaterials (Basel) Date: 2022-05-30 Impact factor: 5.719
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