Combined Photodynamic Thermochemotherapy of Glial Tumors Controlled by MRI and Electronic Sensor (original) (raw)
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The effect of thermotherapy using magnetic nanoparticles on rat malignant glioma
Journal of Neuro-Oncology, 2006
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.
Pharmaceutical Chemistry Journal, 2008
Intravenous administration of dextran-ferrite sol was used to amplify T 2 -weighed echo gradient (500/15) scanning MR images with visualization of the invasion margins of tumor cells into healthy tissues, along with macro-and micrometastases, in animals with lymphocytic leukemia and Ehrlich and Lewis carcinomas. Magnetohydrodynamic thermochemotherapy (MTCT) using a cyclophosphamide-containing magnetic fluid (saturation magnetization (M s ) 8.6 kA/m, pH 7.4, z + 13 mV) at 46°C for 30 min in an alternating magnetic field (0.88 MHz, 7.2 kA/m, 0.15 kW) with aspiration of necrotic material (ANM) produced regression of P388 tumors of volume~110 mm 3 in BDF1 mice prior to metastasis by 40%, with an increase in lifetime (ILT) of 310%; in tumors of volume~330 mm 3 after metastasis and MTCT-ANM with cyclophosphamide pretreatment, ILT was 220%. 157 0091-150X/08/4204-0157
Nanomedicine: Nanotechnology, Biology and Medicine, 2021
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Magnetohydrodynamic thermochemotherapy and MRI of mouse tumors
Journal of Magnetism and Magnetic Materials, 2007
A dextran-ferrite magnetic fluid was successfully tested as magnetic resonance imaging (MRI) contrast agent. The same magnetic fluid was then combined with Melphalan, a chemotherapeutic drug, and used for magnetohydrodynamic thermochemotherapy of different tumors. The placement of the tumors in an AC magnetic field led to hyperthermia at 46 1C for 30 min. In combination with tumor slime aspiration, a 30% regression of 130mm3non−metastaticP388tumorsinBDF1micewasreached,togetherwithalifespanincreaseof290130 mm 3 non-metastatic P388 tumors in BDF 1 mice was reached, together with a life span increase of 290%. The same procedure associated with cyclophosphamide treatment of 130mm3non−metastaticP388tumorsinBDF1micewasreached,togetherwithalifespanincreaseof290500 mm 3 metastases tumor increased the animal's life span by 180%. r (N.A. Brusentsov).
Advances in Optical Technologies, 2008
The objective of this research program is to develop a novel, noninvasive, low-cost infrared (8-12 μm spectral range) imaging technique that would improve upon current methods using nanostructured core/shell magnetic/noble metal-based imaging and therapies. The biocompatible magnetic nanoparticles are able to produce heat under AC magnetic field. This thermal radiation propagates along the tissue by thermal conduction reaching the medium's (tissue's) surface. The surface temperature distribution is acquired by a thermal camera and can be analyzed to retrieve and reconstruct nanoparticles' temperature and location within the tissue. The technique may function as a diagnostic tool thanks to the ability of specific bioconjugation of these nanoparticles to tumor's outer surface markers. Hence, by applying a magnetic field, we could cause a selective elevation of temperature of the targeted nanoparticles up to 5 • C, which detects the tumor. Furthermore, elevating the temperature over 65 • C and up to 100 • C stimulates a thermo ablating interaction which causes a localized irreversible damage to the cancerous site with no harm to the surrounding tissue. While functioning as a diagnostic tool, this procedure may serve as a targeted therapeutic tool under thermal feedback control as well.
Journal of Neuro-Oncology, 2006
We aimed to evaluate the feasibility and tolerability of the newly developed thermotherapy using magnetic nanoparticles on recurrent glioblastoma multiforme. Fourteen patients received 3-dimensional image guided intratumoral injection of aminosilane coated iron oxide nanoparticles. The patients were then exposed to an alternating magnetic field to induce particle heating. The amount of fluid and the spatial distribution of the depots were planned in advance by means of a specially developed treatment planning software following magnetic resonance imaging (MRI). The actually achieved magnetic fluid distribution was measured by computed tomography (CT), which after matching to pre-operative MRI data enables the calculation of the expected heat distribution within the tumor in dependence of the magnetic field strength.
Glial brain tumor targeting of magnetite nanoparticles in rats
Journal of Magnetism and Magnetic Materials, 2001
After intravenous injection into rats, nanodispersed iron preparations accumulated in internal organs but not in the brain. Hyperosmotic blood}brain barrier disruption followed by injection of magnetite}dextran nanoparticles into the carotid artery resulted in penetration of particles into the brain tumor and peritumoral tissue of the rats bearing glial brain tumor and T-weighted magnetic resonance imaging (MRI) images showed pronounced signal loss in the tumor region.
Magnetic Nanoparticles for Tumor Imaging and Therapy: A So-Called Theranostic System
Pharmaceutical Research, 2013
In this review, we discussed the establishment of a so-called "theranostic" system by instituting the basic principles including the use of: [1] magnetic iron oxide nanoparticles (MION)-based drug carrier; [2] intra-arterial (I.A.) magnetic targeting; [3] macromolecular drugs with unmatched therapeutic potency and a repetitive reaction mechanism; [4] cell-penetrating peptide-mediated cellular drug uptake; and [5] heparin/protamine-regulated prodrug protection and tumor-specific drug re-activation into one single drug delivery system to overcome all possible obstacles, thereby achieving a potentially non-invasive, magnetic resonance imaging-guided, clinically enabled yet minimally toxic brain tumor drug therapy. By applying a topography-optimized I.A. magnetic targeting to dodge rapid organ clearance of the carrier during its first passage into the circulation, tumor capture of MION was enriched by >350 folds over that by conventional passive enhanced permeability and retention targeting. By adopting the prodrug strategy, we observed by far the first experimental success in a rat model of delivering micro-gram quantity of the large β-galactosidase model protein selectively into a brain tumor but not to the ipsi-or contra-lateral normal brain regions. With the therapeutic regimens of most toxin/siRNA drugs to fully (>99.9%) eradicate a tumor being in the nano-molar range, the prospects of reaching this threshold become practically accomplishable.
Einstein (São Paulo), 2012
OBJECTIVE: To assess intracellular labeling and quantification by magnetic resonance imaging using iron oxide magnetic nanoparticles coated with biocompatible materials in rat C6 glioma cells in vitro. These methods will provide direction for future trials of tumor induction in vivo as well as possible magnetic hyperthermia applications. METHODS: Aminosilane, dextran, polyvinyl alcohol, and starch-coated magnetic nanoparticles were used in the qualitative assessment of C6 cell labeling via light microscopy. The influence of the transfection agent poly-L-lysine on cellular uptake was examined. The quantification process was performed by relaxometry analysis in T1 and T2weighted phantom images. RESULTS: Light microscopy revealed that the aminosilane-coated magnetic nanoparticles alone or complexed with poly-L-lysine showed higher cellular uptake than did the uncoated magnetic particles. The relaxivities of the aminosilane-coated magnetic nanoparticles with a hydrodynamic diameter of 5...
18 F-FET PET for planning of thermotherapy using magnetic nanoparticles in recurrent glioblastoma
International Journal of Hyperthermia, 2006
Purpose: Thermotherapy using magnetic nanoparticles (nano cancer therapy) is a new concept of local tumour therapy, which is based on controlled heating of intra-tumoural injected magnetic nanoparticles. The aim of this study was to evaluate the usefulness of PET with a recently introduced amino acid tracer O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) for targeting the nanoparticles implantation. Materials and methods: Eleven patients with glioblastoma recurrences underwent MR and FET-PET imaging for planning of the nano cancer therapy. Thereafter, the gross tumour volumes (GTV) were defined, taking into consideration the results of both imaging tools. Results: The MRI-based mean GTV was 24.3 cm 3 (range 2.5-59.7) and the PET-based mean GTV 31.9 cm 3 (range 5.2-77.9). On the average the MRI identified an additional 8.9 AE 4.7 cm 3 and the FET-PET scan-an additional 16.5 AE 15.2 cm 3 outside of the common GTV (15.4 AE 11.0 cm 3 ). The mean final GTV accounted to 33.8 cm 3 (range, 5.2-77.9). The additional information of FET-PET led to an increase in GTV by 22-286% in eight patients and to a decrease of 23% and 26%, respectively, in two patients. In one patient, the final GTV was defined on the basis of MRI data only. Conclusions: FET-PET adds important information on the actual tumour volume in recurrent glioblastomas and is highly valuable for defining the target volume for the nano cancer therapy.