Browsing by Author "Engels, E"

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    First extensive study of lanthanum manganite nanoparticles to target deadly brain cancer
    (Australian Institute of Nuclear Science and Engineering (AINSE), 2020-11-11) Khochaiche, A; Westlake, M; O'Keefe, A; Engels, E; Li, N; Vogel, S; Valceski, M; Konstantinov, K; Corde, S; Lerch, MLF; Tehei, M; Rule, KC; Horvat, J
    The ability to successfully target deep-seated tumours in sensitive areas of the body is limited to adequate targeting strategies. More specifically, brain and central nervous system (CNS) cancers can be the most aggressive, have higher mortality rates and lower accessibility to chemotherapeutic drugs. A proposed solution to target these concerns is through introducing high atomic number (Z) nanoparticles (NPs) such as silver-doped lanthanum manganite (LAGMO) to aid in common treatments such as radiation therapy. These NPs can bypass the blood brain barrier and are capable of increasing the damage from the radiation due to their high-Z. Most importantly they have potential to cause cancer cells to undergo hyperthermia (a cell death precursor) as the NPs heat up in their environment due to their Curie temperature being in the hyperthermia range of interest.
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    First extensive study of silver-doped lanthanum manganite nanoparticles for inducing selective chemotherapy and radio-toxicity enhancement
    (Elsevier B. V., 2021-04) Khochaiche, A; Westlake, M; O'Keefe, A; Engels, E; Vogel, S; Valceski, M; Li, N; Rule, KC; Horvat, J; Konstantinov, K; Rosenfeld, AB; Lerch, MLF; Corde, S; Tehei, M
    Nanoparticles have a great potential to increase the therapeutic efficiency of several cancer therapies. This research examines the potential for silver-doped lanthanum manganite nanoparticles to enhance radiation therapy to target radioresistant brain cancer cells, and their potential in combinational therapy with magnetic hyperthermia. Magnetic and structural characterisation found all dopings of nanoparticles (NPs) to be pure and single phase with an average crystallite size of approximately 15 nm for undoped NPs and 20 nm for silver doped NPs. Additionally, neutron diffraction reveals that La0.9Ag0.1MnO3 (10%-LAGMO) NPs exhibit residual ferromagnetism at 300 K that is not present in lower doped NPs studied in this work, indicating that the Curie temperature may be manipulated according to silver doping. This radiobiological study reveals a completely cancer-cell selective treatment for LaMnO3, La0.975Ag0.025MnO3 and La0.95Ag0.05MnO3 (0, 2.5 and 5%-LAGMO) and also uncovers a potent combination of undoped lanthanum manganite with orthovoltage radiation. Cell viability assays and real time imaging results indicated that a concentration of 50 μg/mL of the aforementioned nanoparticles do not affect the growth of Madin-Darby Canine Kidney (MDCK) non-cancerous cells over time, but stimulate its metabolism for overgrowth, while being highly toxic to 9L gliosarcoma (9LGS). This is not the case for 10%-LAGMO nanoparticles, which were toxic to both non-cancerous and cancer cell lines. The nanoparticles also exhibited a level of toxicity that was regulated by the overproduction of free radicals, such as reactive oxygen species, amplified when silver ions are involved. With the aid of fluorescent imaging, the drastic effects of these reactive oxygen species were visualised, where nucleus cleavage (an apoptotic indicator) was identified as a major consequence. The genotoxic response of this effect for 9LGS and MDCK due to 10%-LAGMO NPs indicates that it is also causing DNA double strand breaks within the cell nucleus. Using 125 kVp orthovoltage radiation, in combination with an appropriate amount of NP-induced cell death, identified undoped lanthanum manganite as the most ideal treatment. Real-time imaging following the combination treatment of undoped lanthanum manganite nanoparticles and radiation, highlighted a hinderance of growth for 9LGS, while MDCK growth was boosted. The clonogenic assay following incubation with undoped lanthanum manganite nanoparticles combined with a relatively low dose of radiation (2 Gy) decreased the surviving fraction to an exceptionally low (0.6 ± 6.7)%. To our knowledge, these results present the first biological in-depth analysis on silver-doped lanthanum manganite as a brain cancer selective chemotherapeutic and radiation dose enhancer and as a result will propel its first in vivo investigation. © 2021 Elsevier B.V.
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    Incorporating clinical imaging into the delivery of microbeam radiation therapy
    (MDPI, 2021-09-30) Paino, JR; Barnes, M; Engels, E; Davis, JA; Guatelli, S; de Veer, M; Hall, CJ; Häusermann, D; Tehei, M; Corde, S; Rosenfeld, AB; Lerch, MLF
    Synchrotron microbeam radiation therapy is a promising pre-clinical radiation treatment modality; however, it comes with many technical challenges. This study describes the image guidance protocol used for Australia’s first long-term pre-clinical MRT treatment of rats bearing 9L gliosarcoma tumours. The protocol utilises existing infrastructure available at the Australian Synchrotron and the adjoining Monash Biomedical Imaging facility. The protocol is designed and optimised to treat small animals utilising high-resolution clinical CT for patient specific tumour identification, coupled with conventional radiography, using the recently developed SyncMRT program for image guidance. Dosimetry performed in small animal phantoms shows patient dose is comparable to standard clinical doses, with a CT associated dose of less than 1.39cGy and a planar radiograh dose of less than 0.03cGy. Experimental validation of alignment accuracy with radiographic film demonstrates end to end accuracy of less than ±0.34mm in anatomical phantoms. Histological analysis of tumour-bearing rats treated with microbeam radiation therapy verifies that tumours are targeted well within applied treatment margins. To date, this technique has been used to treat 35 tumour-bearing rats. © 2021 by the Authors. Licensee MDPI, Basel, Switzerland.
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    A novel anthropomorphic phantom composed of tissue-equivalent materials for use in experimental radiotherapy: design, dosimetry and biological pilot study
    (MDPI, 2023-04-26) Breslin, T; Paino, JR; Wegner, M; Engels, E; Fiedler, S; Forrester, HB; Rennau, H; Bustillo, J; Cameron, M; Häusermann, D; Hall, CJ; Krause, D; Hildebrandt, G; Lerch, MLF; Schültke, E
    The production of anthropomorphic phantoms generated from tissue-equivalent materials is challenging but offers an excellent copy of the typical environment encountered in typical patients. High-quality dosimetry measurements and the correlation of the measured dose with the biological effects elicited by it are a prerequisite in preparation of clinical trials with novel radiotherapy approaches. We designed and produced a partial upper arm phantom from tissue-equivalent materials for use in experimental high-dose-rate radiotherapy. The phantom was compared to original patient data using density values and Hounsfield units obtained from CT scans. Dose simulations were conducted for broad-beam irradiation and microbeam radiotherapy (MRT) and compared to values measured in a synchrotron radiation experiment. Finally, we validated the phantom in a pilot experiment with human primary melanoma cells. © 2023 The Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) licence.
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    The spinal cord as organ of risk: assessment for acute and subacute neurological adverse effects after microbeam radiotherapy in a rodent model
    (MDPI, 2023-04-26) Jaekel, F; Paino, JR; Engels, E; Klein, M; Barnes, M; Häusermann, D; Hall, CJ; Zheng, G; Wang, HX; Hildebrandt, G; Lerch, MLF; Schültke, E
    Microbeam radiotherapy (MRT), a high dose rate radiotherapy technique using spatial dose fractionation at the micrometre range, has shown a high therapeutic efficacy in vivo in different tumour entities, including lung cancer. We have conducted a toxicity study for the spinal cord as organ of risk during irradiation of a target in the thoracic cavity. In young adult rats, the lower thoracic spinal cord was irradiated over a length of 2 cm with an array of quasi-parallel microbeams of 50 µm width, spaced at a centre-to-centre distance of 400 µm, with MRT peak doses up to 800 Gy. No acute or subacute adverse effects were observed within the first week after irradiation up to MRT peak doses of 400 Gy. No significant differences were seen between irradiated animals and non-irradiated controls in motor function and sensitivity, open field test and somatosensory evoked potentials (SSEP). After irradiation with MRT peak doses of 450–800 Gy, dose-dependent neurologic signs occurred. Provided that long-term studies do not reveal significant morbidity due to late toxicity, an MRT dose of 400 Gy can be considered safe for the spinal cord in the tested beam geometry and field size. © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.