Invited Paper
Magnetic fluid hyperthermia (MFH): Cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles

https://doi.org/10.1016/S0304-8853(99)00088-8Get rights and content

Abstract

The story of hyperthermia with small particles in AC magnetic fields started in the late 1950s, but most of the studies were unfortunately conducted with inadequate animal systems, inexact thermometry and poor AC magnetic field parameters, so that any clinical implication was far behind the horizon.

More than three decades later, it was found, that colloidal dispersions of superparamagnetic (subdomain) iron oxide nanoparticles exhibit an extraordinary specific absorption rate (SAR [W/g]), which is much higher at clinically tolerable H0f combinations in comparison to hysteresis heating of larger multidomain particles. This was the renaissance of a cancer treatment method, which has gained more and more attention in the last few years. Due to the increasing number of randomized clinical trials preferentially in Europe with conventional E-field hyperthermia systems, the general medical and physical experience in hyperthermia application is also rapidly growing. Taking this increasing clinical experience carefully into account together with the huge amount of new biological data on heat response of cells and tissues, the approach of magnetic fluid hyperthermia (MFH) is nowadays more promising than ever before. The present contribution reviews the current state of the art and some of the future perspectives supported by advanced methods of the so-called nanotechnology.

Section snippets

Basic principles of hyperthermia

Heating of certain organs or tissues to temperatures between 41°C and 46°C preferentially for cancer therapy is called `Hyperthermia'. Higher temperatures up to 56°C, which yield widespread necrosis, coagulation or carbonization (depending on temperature) is called `thermo-ablation'. Both mechanisms act completely different concerning biological response and application technique. The `classical’ hyperthermia induces almost reversible damage to cells and tissues, but as an adjunct it enhances

Clinical hyperthermia

State-of-the-art radiofrequency (RF-) hyperthermia systems, e.g. annular phased array systems (APAS) for regional hyperthermia of deep seated tumors, are still limited by the known heterogeneity of tissue electrical conductivities or high perfused tissues, which makes selective heating of those regions with such E-field dominant systems very difficult. Further application techniques are whole body hyperthermia (WBH, with water-filtered infra-red irradiation), local hyperthermia (e.g. with

Much more than simple particle heating: the biological concept of magnetic fluid hyperthermia (MFH)

In the early 1960s, a few US groups were the first, who tried to perform hyperthermia with magnetizable microparticles, which were heated by an externally applied AC magnetic field. The use of H-field dominant systems together with power absorbing material instead of power steering of E-field dominant systems is therefore an old idea. However, before the early nineties, the status of this research was diffuse and clinical application was unthinkable. Poor defined animal systems [18] or ex vivo

Recent results

In order to proceed from the encouraging results with the mammary carcinoma of the mouse, more animal experiments are required to fix the current state of MFH as an almost site-specific modality, which allows regional heating in different locations of the body. As a precondition, the technology of AC magnetic field application is currently under development [24]. If an almost regional AC magnetic field application could be realized, migration of any ferrofluid to distant locations could be

Perspectives

It is still a fascinating concept, that tumor cells could be loaded with thousands of particles, which would become activated – comparable to genes – only by a specific signal, yielding the death of all particle containing cells as soon as an AC magnetic field is applied. Our cellular observations so far indicate that a tumor, which has taken up these particles, will not be able to get rid of them. Daughter cells from a particle containing parent cells should therefore contain up to 50% of the

Acknowledgements

The authors wish to thank Mrs. Lajoux and Prof. Schnoy of the Department of Electron Microscopy and Prof. Maier-Hauff of the Department of Neurosurgery, both of the University Clinic Charité, for valuable co-operation and helpful discussions. This project is supported by the Deutsche Forschungsgemeinschaft (DFG), Sonderforschungsbereich 273 (TP A8), Bonn, Germany.

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