Browsing by Author "Barnes, M"

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    Gd-TPP-DOTA reduces cell viability in cancer cells via synchrotron radiotherapy
    (Australian National University, 2021-08-24) Middleton, RJ; Howell, NR; Livio, E; Wyatt, NA; Chacon, A; Fraser, BH; Barnes, M; Cameron, M; Rendina, LM; Häusermann, D; Lerch, MLF; Safavi-Naeini, M
    High-Z elements have been proposed as radiosensitisers in X-ray photon radiotherapy due to their emission of multiple high-LET photo- and Auger electrons following X-ray irradiation. Gadolinium is a particularly attractive candidate radiosensitiser, since it can also be used as an MRI contrast agent. In this study, we report on the efficacy of Gd-triphenylphosphonium salt-DOTA (Gd(III)-TPP-DOTA) for synchrotron microbeam radiation therapy dose enhancement. The compound utilises the mitochondrial targeting moiety triphenylphosphonium (TPP) to accumulate Gd in the inner mitochondrial membrane. Experiments were conducted using the dynamic mode option at hutch 2B of the Imaging and Medical Beamline at the Australian Synchrotron. Human glioblastoma multiforme cells (T98G cell line) were cultured to 80-90% confluence in T12.5 flasks. Approximately 24 hours prior to irradiation, the cultures were either treated with a 500 μM solution of Gd(III)DOTA-TPP or a vehicle control. Spatial dose distribution of synchrotron broad beam (BB) and single/multiple microbeams were measured using a micron-scale X-Tream dosimetry system and Gafchromic films in air and at 2 cm depth in solid water (same depth as the monolayer of cells in T12.5 flasks). A total of 96 flasks were irradiated, with doses of 0, 1, 2, 3, 4, 5, 10 and 16 Gy delivered in valley (MRT) or uniformly (BB). Post irradiation, each flask was re-seeded into 7 x 96 well-plates to perform the resazurin cell proliferation assay up to 7 days after irradiation. Our preliminary analysis indicates that for cells irradiated by 3 Gy of BB or MRT radiation, the addition of Gd(III)DOTA-TPP results in a reduction in viable cell mass by 24.25% and 25.79%, respectively, compared with untreated flasks. © The Authors
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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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    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.