Zusammenfassung
Die Strategien zur Therapie von Brustkrebs befinden sich in einem Wandel, insbesondere solche, die auf den Einsatz bei der Behandlung von frühen, prognostisch günstigen Tumorstadien abzielen. Eine potenzielle minimalinvasive Therapieform besteht in der Anreicherung eines verträglichen magnetischen Materials (Eisenoxid, speziell Magnetit) im Zielgewebe. Durch Anlegen eines magnetischen Wechselfeldes wird dann am Tumorort gezielt Energie absorbiert und in zellschädigende Wärme umgewandelt. In vorliegender Übersichtsdarstellung werden die für die magnetische Thermotherapie notwendigen Rahmenbedingungen und Einflussgrößen anhand von tierexperimentellen in-vitro- und in-vivo-Untersuchungen vorgestellt und Extrapolationen in Bezug auf die klinische Anwendung diskutiert. Insbesondere werden das Wärmepotenzial des magnetischen Materials, die Wahl der Parameter des magnetischen Wechselfeldes, das Auftreten von Wirbelströmen, die Generierung von lokalisierten Wärmestellen sowie die zu erwartenden Temperaturanstiege und deren Effekte am Tumorort behandelt.
Abstract
The therapeutic strategy for breast cancer is changing, especially for early tumor stages with good prognosis. One potential minimally invasive therapy modality consists in the accumulation of a well-tolerated magnetic material (iron oxides, particularly magnetite) in the target tissue. By applying an alternating magnetic field, energy is selectively absorbed and induces harmful heating of the tumor. The present review deals with the essential conditions and parameters as studied in vitro and in vivo in animal experiments. Extrapolations to the clinical situation are discussed, in particular, the heating potential of the magnetic material, the selection of the magnetic field parameters, the occurrence of eddy currents, the generation of localized heating spots and the expected temperature rises and their effects on the tumor area.
Key words
Minimal invasive therapy - breast carcinoma - hyperthermia - magnetic thermoablation - magnetic nanoparticles - magnetite
Literatur
1
Mahnken A H, Tacke J, Bücker A. et al .
Perkutane Radiofrequenzablation maligner Leberläsionen: Erste Erfahrungen mit einem 200-W-Generator.
Fortschr Röntgenstr.
2002;
174
216-223
2
Harries S A, Amin Z, Smith M E. et al .
Interstitial laser photocoagulation as a treatment for breast cancer.
The Britisch Journal of Surgery.
1994;
81
1617-1619
3
Dowlatshahi K, Fan M, Gould V E. et al .
Stereotactically guided laser therapy of occult breast tumors.
Archives of Surgery.
2000;
135
1345-1352
4
Harari P M, Hynynen K H, Roemer R B. et al .
Development of scanned focused ultrasound hyperthermia: clinical response evaluation.
International Journal of Radiation Oncology Biology Physics.
1991;
21
831-840
5
Jeffrey S S, Birdwell R L, Ikeda D M. et al .
Radiofrequency ablation of breast cancer: first report of an emerging technology.
Archives of Surgery.
1999;
134
1064-1068
6
Okon E, Pouliquen D, Okon P. et al .
Biodegradation of magnetite dextran nanoparticles in the rat. A histologic and biophysical study.
Laboratoy Investigation.
1994;
71
895-903
7
Hergt R, Andrä W, d’Ambly C G. et al .
Physical limits of hyperthermia using magnetite fine particles.
IEEE-Transactions on Magnetics.
1998;
34
3745-3754
8
Hergt R, Hiergeist R, Hilger I. et al .
Magnetic Nanoparticles for Thermoablation.
Recent Research Developments in Material Science.
2002;
3
723-742
9 Shliomis M I, Stepanov V I. Theory of the Dynamic Susceptibility of Magnetic Fluids. Coffey W Relaxation Phenomena in Condensed Matter New York; Wiley 1994: 1-30
10 Andrä W. Magnetic hyperthermia. Andrä W, Nowak H Magnetism in Medicine Berlin; Wiley-VCH 1998: 455-470
11
Hergt R, Hiergeist R, Hilger I. et al .
Maghemite nanoparticles with very high ac-losses for application in rf-magnetic hyperthermia.
Journal of Magnetism and Magnetic Materials.
2004;
270
345-347
12
Raj K, Moskowitz B, Casciari R.
Advances in ferrofluid technology.
Journal of Magnetism and Magnetic Materials.
1995;
149
174-180
13
Alexiou C, Arnold W, Klein R J. et al .
Locoregional cancer treatment with magnetic drug targeting.
Cancer Research.
2000;
60
6641-6648
14
Lübbe A S, Bergemann C, Riess H. et al .
Clinical experiences with magnetic drug targeting: a phase I study with 4’epidoxorubicin in 14 patients with advanced solid tumors.
Cancer Research.
1996;
56
4686-4693
15
Taupitz M, Schmitz S, Hamm B.
Superparamagnetische Eisenoxidpartikel: Aktueller Stand und zukünftige Entwicklungen.
Fortschr Röntgenstr.
2003;
175
752-765
16
Hilger I, Andrä W, Hergt R. et al .
Electromagnetic heating of breast tumors in interventional radiology: in vitro and in vivo studies in human cadavers and mice.
Radiology.
2001;
218
570-575
17
Hilger I, Hiergeist R, Hergt R. et al .
Thermoablation of tumors using magnetic nanoparticles: an in vivo feasibility study.
Investigative Radiology.
2002;
37
580-586
18
Hilger I, Kießling A, Romanus E. et al .
Magnetic nanoparticles for selective detection and heating of magnetically labeled cells in culture: preliminary investigation.
Nanotechnology.
2004;
15
1027-1032
19
Bacon B R, Stark D D, Park C H. et al .
Ferrite particles: a new magnetic resonance imaging contrast agent. Lack of acute or chronic hepatoxicity after intravenous administration.
The Journal of Laboratory and Clinical Medicine.
1987;
110
164-171
20
Marchal G, van Heke P, Demaerel P. et al .
Detection of liver metastases with superparamagnetic iron oxide in 15 patients; results of MR imaging at 1.5 T.
American Journal of Radiology.
1988;
152
771-775
21
Rummeny E, Weissleder R, Stark D D. et al .
Kernspintomographie fokaler Leber- und Milzläsionen.
Radiologe.
1988;
28
380-386
22
Beyersdorff D, Taupitz M, Giessing M. et al .
Staging von Harnblasentumoren in der MRT: Wertigkeit der intravesikalen Applikation von eisenoxidhaltigem Kontrastmittel in Kombination mit hochaufgelöster T2-gewichteter Bildgebung.
Fortschr Röntgenstr.
2000;
172
504-508
23
Axmann C, Bohndorf K, Gellissen J. et al .
Vergleich zwischen GE- und SE-Sequenzen in der MRT nach i. v. Applikation von superparamagnetischen Eisenpartikeln bei der Beurteilung von experimentell induzierten Osteosarkomen der Weichteile.
Fortschr Röntgenstr.
1997;
166
146-152
24
Hilger I, Frühauf S, Linß W. et al .
Cytotoxicity of selected magnetic ferrofluids on human adenocarcinoma cells.
Journal of Magnetism and Magnetic Materials.
2003;
261
7-12
25
Laniado M, Chachuat A.
Verträglichkeitsprofil von ENDOREM.
Radiologe.
1995;
35
266-270
26
Hilger I, Hofmann F, Reichenbach J R. et al .
Bildgebende Darstellung von Magnetiten in vitro.
Fortschr Röntgenstr.
2002;
173
101-103
27
Lwakatare F, Yamashita Y, Nakayama M. et al .
SPIO-enhanced MR imaging of focal fatty liver lesions.
Abdominal Imaging.
2001;
26
157-160
28
Tacke J.
Perkutane Radiofrequenzablation - klinische Indikationen und Ergebnisse.
Fortschr Röntgenstr.
2003;
175
156-168
29
Chen L, Wansapura J P, Heit G. et al .
Study of laser ablation in the in vivo rabbit brain with MR thermometry.
Journal of Magnetic Resonance Imaging.
2002;
16
147-152
30
Weidensteiner C, Quesson B, Caire-Gana B. et al .
Real-time MR temperature mapping of rabbit liver in vivo during thermal ablation.
Magnetic Resonance in Medicine.
2003;
50
322-330
31
Germain D, Chevallier P, Laurent A. et al .
MR monitoring of tumour thermal therapy.
MAGMA.
2001;
13
47-59
32
Brezovich I.
Low frequency hyperthermia: capacitive and ferromagnetic thermoseed methods. In: Palival P, Hetzel FW (eds).
Medical Physics Monograph.
1988;
16
82
33 Hill R P, Hunt J W. Hyperthermia. Tannock JF, Hill RP The Basic Science of Oncology New York; Pergamon Press 1987: 337-357
34 Hall E J. Hyperthermia. Hall EJ Radiobiology for the Radiologist. Fourth Edition Philadelphia; J.B. Lippincott Company 1994: 257-288
35
Mills M D, Meyn R E.
Hyperthermic potentiation of unrejoined DNA strand breaks following irradiation.
Radiation Research.
1983;
95
327-338
36
Hilger I, Frühauf S, Andrä W. et al .
Magnetic heating as a therapeutic tool.
Thermology International.
2001;
11
130-136
37
Hilger I, Rapp A, Greulich K O. et al .
Assessment of DNA damages on target in tumor cells after thermoablative heating.
Radiology (in press).
38
Heisterkamp J, van Hillegersberg R, IJzermans J NM.
Critical temperature and heating time for coagulation damage: implications for interstitial laser coagulation (ILC) of tumors.
Lasers in Surgery and Medicine.
1999;
25
257-262
39
Ritchie K P, Keller B M, Syed K M. et al .
Hyperthermia (heat-shock) induced protein denaturation in liver, muscle and lens tissue as determined by differential scanning calorimetry.
International Journal of Hyperthermia.
1994;
10
605-618
40
Xu Y, Qian R.
Analysis of thermal injury process based on enzyme deactivation mechanisms.
Journal of Biomechanical Engineering - Transactions of the ASME.
1995;
117
462-465
41 Joly M A. (ed) .A physico-chemical approach to the denaturation of proteins. London; Academic Press Vol 1965: 1-350
42
Andrä W, d’Ambly C G, Hergt R. et al .
Temperature distribution as function of time around a small spherical heat source of local magnetic hyperthermia.
Journal of Magnetism and Magnetic Materials.
1999;
194
197-203
43
Hilger I, Hergt R, Kaiser W A.
Effects of magnetic thermoablation in muscle tissue using iron oxide particles. An in vitro study.
Investigative Radiology.
2000;
35
170-179
44
Allgaier H P, Rossi S, Deibert P. et al .
Hepatocellular carcinoma: percutaneous ethanol injection/transarterial chemoembolization/radiofrequency thermoablation.
Schweizerische Rundschau für Medizin Praxis.
2000;
89
1056-1060
45
Rossi S, Garbagnati F, Lencioni R. et al .
Percutaneous radiofrequency thermal ablation of nonresectable hepatocellular carcinoma after occlusion of tumor blood supply.
Radiology.
2000;
217
119-126
46
Bicher H I, Hetzel F W, Sandhu T S. et al .
Effects of hyperthermia on normal and tumor microenvironment.
Radiology.
1980;
137
523-530
47
Böhm T, Malich A, Goldberg S N. et al .
Vacuum assisted resection of breast cancer with and without subsequent radiofrequency ablation: Feasibility of complete tumor treatment tested in an animal model.
Journal of Vascular Interventional Radiology.
2001;
12
1086-1093
48
Böhm T, Hilger I, Müller W. et al .
Saline-enhanced radiofrequency ablation of breast tissue. An in vitro feasibility study.
Investigative Radiology.
2000;
35
149-157
49
Corica F A, Cheng L, Ramnani D. et al .
Transurethral hot-water balloon thermoablation for benign prostatic hyperplasia: patient tolerance and pathologic findings.
Urology.
2000;
56
76-81
50
Larson T R, Bostwick D G, Corica A.
Temperature-correlated histopathologic changes following microwave thermoablation of obstructive tissue in patients with benign prostatic hyperplasia.
Urology.
1996;
47
463-469
51
Pichler L, Anzböck W, Pärtan G. et al .
Radiofrequenz-Thermoablation maligner Raumforderungen der Leber.
Fortschr Röntgenstr.
2002;
174
1369-1374
52 Riede U N, Schaefer H E. Physikalische Zellschädigung. Riede UN, Schaefer HE Allgemeine und Spezielle Pathologie Stuttgart; Georg Thieme Verlag 1995: 154-167
53
Jordan A, Scholz R, Wust P. et al .
Effects of Magnetic Fluid Hyperthermia (MFH) on C3H mammary carcinoma in vivo.
International Journal of Hyperthermia.
1997;
13
587-605
54
Weissleder R, Stark D D, Engelstad B L. et al .
Superparamagnetic iron oxide: pharmacokinetics and toxicity.
Am J of Roentgenol.
1989;
152
167-173
PD Dr. Ingrid Hilger
Institut für Diagnostische und Interventionelle Radiologie des Klinikums der Friedrich-Schiller-Universität Jena, Forschungszentrum Lobeda
07740 Jena
Germany
Phone: ++ 49/36 41/9 32 59 21
Fax: ++ 49/36 41/9 32 59 22
Email: ingrid.hilger@med.uni-jena.de