title: The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma.
abstract: Thermotherapy using magnetic nanoparticles is a new technique for interstitial hyperthermia and thermoablation based on magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. To evaluate the potential of this technique for minimally invasive treatment, we carried out a systematic analysis of its effects on experimental glioblastoma multiforme in a rat tumor model. Tumors were induced by implantation of RG-2-cells into the brains of 120 male Fisher rats. Animals were randomly allocated to 10 groups of 12 rats each, including controls. Animals received two thermotherapy treatments following a single intratumoral injection of two different magnetic fluids (dextran- or aminosilane-coated iron-oxide nanoparticles). Treatment was carried out on days four and six after tumor induction using an alternating magnetic field applicator system operating at a frequency of 100 kHz and variable field strength of 0-18 kA/m. The effectiveness of treatment was determined by the survival time of the animals and histopathological examinations of the brain and the tumor.Thermotherapy with aminosilane-coated nanoparticles led up to 4.5-fold prolongation of survival over controls, while the dextran-coated particles did not indicate any advantage. Intratumoral deposition of the aminosilane-coated particles was found to be stable, allowing for serial thermotherapy treatments without repeated injection. Histological and immunohistochemical examinations after treatment revealed large necrotic areas close to particle deposits, a decreased proliferation rate and a reactive astrogliosis adjacent to the tumor.Thus, localized interstitial thermotherapy with magnetic nanoparticles has an antitumoral effect on malignant brain tumors. This method is suitable for clinical use and may be a novel strategy for treating malignant glioma, which cannot be treated successfully today. The optimal treatment schedules and potential combinations with other therapies need to be defined in further studies.
authors.affiliation: Center of Biomedical Nanotechnology (CBN), c/o Department of Radiology, CVK, Charité--University Medicine, Berlin, Germany. andreas.jordan@charite.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Jordan
authors.forename: Regina
authors.initials: R
authors.lastname: Scholz
authors.forename: Klaus
authors.initials: K
authors.lastname: Maier-Hauff
authors.forename: Frank K H
authors.initials: FK
authors.lastname: van Landeghem
authors.forename: Norbert
authors.initials: N
authors.lastname: Waldoefner
authors.forename: Ulf
authors.initials: U
authors.lastname: Teichgraeber
authors.forename: Jens
authors.initials: J
authors.lastname: Pinkernelle
authors.forename: Harald
authors.initials: H
authors.lastname: Bruhn
authors.forename: Fabian
authors.initials: F
authors.lastname: Neumann
authors.forename: Burghard
authors.initials: B
authors.lastname: Thiesen
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Roland
authors.initials: R
authors.lastname: Felix
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005910:Glioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006979:Hyperthermia, Induced; D007150:Immunohistochemistry; D008279:Magnetic Resonance Imaging; D008280:Magnetics / Q000627:therapeutic use; D008297:Male; D049329:Nanostructures; D051381:Rats; D011916:Rats, Inbred F344; D016019:Survival Analysis