Gd-TPP-DOTA reduces cell viability in cancer cells via synchrotron radiotherapy

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dc.contributor.authorMiddleton, RJen_AU
dc.contributor.authorHowell, NRen_AU
dc.contributor.authorLivio, Een_AU
dc.contributor.authorWyatt, NAen_AU
dc.contributor.authorChacon, Aen_AU
dc.contributor.authorFraser, BHen_AU
dc.contributor.authorBarnes, Men_AU
dc.contributor.authorCameron, Men_AU
dc.contributor.authorRendina, LMen_AU
dc.contributor.authorHäusermann, Den_AU
dc.contributor.authorLerch, Men_AU
dc.contributor.authorSafavi-Naeini, Men_AU
dc.date.accessioned2024-04-09T01:46:20Zen_AU
dc.date.available2024-04-09T01:46:20Zen_AU
dc.date.issued2021-08-24en_AU
dc.date.statistics2023-04-24en_AU
dc.description.abstractHigh-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 Authorsen_AU
dc.identifier.citationMiddleton, R., Howell. N., Livio. E., Wyatt, N., Chacon, A., Fraser, B., Barnes, M., Cameron, M., Rendina, L., Hausermann, D., Lerch, M., & Safavi-Naeini, M. (2021). Gd-TPP-DOTA reduces cell viability in cancer cells via synchrotron radiotherapy, Presentation to the ANSTO User Meeting, 24-26 November 2021, Online. Retrieved from: https://events01.synchrotron.org.au/event/146/contributions/4266/contribution.pdfen_AU
dc.identifier.conferenceenddate2021-11-26en_AU
dc.identifier.conferencenameANSTO User Meetingen_AU
dc.identifier.conferenceplaceOnlineen_AU
dc.identifier.conferencestartdate2021-11-24en_AU
dc.identifier.urihttps://events01.synchrotron.org.au/event/146/contributions/4266/contribution.pdfen_AU
dc.identifier.urihttps://apo.ansto.gov.au/handle/10238/15552en_AU
dc.language.isoenen_AU
dc.publisherAustralian National Universityen_AU
dc.subjectNeoplasmsen_AU
dc.subjectSynchrotron radiationen_AU
dc.subjectX-ray photoelectron spectroscopyen_AU
dc.subjectElectronsen_AU
dc.subjectIrradiationen_AU
dc.subjectTheraphyen_AU
dc.subjectGadoliniumen_AU
dc.subjectANSTOen_AU
dc.subjectAustralian organizationsen_AU
dc.subjectDosimetryen_AU
dc.titleGd-TPP-DOTA reduces cell viability in cancer cells via synchrotron radiotherapyen_AU
dc.typeConference Presentationen_AU
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