title: Optimizing dose enhancement with Ta2O5nanoparticles for synchrotron microbeam activated radiation therapy.
abstract: Microbeam Radiation Therapy (MRT) exploits tumour selectivity and normal tissue sparing with spatially fractionated kilovoltage X-ray microbeams through the dose volume effect. Experimental measurements with Ta2O5nanoparticles (NPs) in 9L gliosarcoma treated with MRT at the Australian Synchrotron, increased the treatment efficiency. Ta2O5NPs were observed to form shells around cell nuclei which may be the reason for their efficiency in MRT. In this article, our experimental observation of NP shell formation is the basis of a Geant4 radiation transport study to characterise dose enhancement by Ta2O5NPs in MRT. Our study showed that NP shells enhance the physical dose depending microbeam energy and their location relative to a single microbeam. For monochromatic microbeam energies below ∼70keV, NP shells show highly localised dose enhancement due to the short range of associated secondary electrons. Low microbeam energies indicate better targeted treatment by allowing higher microbeam doses to be administered to tumours and better exploit the spatial fractionation related selectivity observed with MRT. For microbeam energies above ∼100keV, NP shells extend the physical dose enhancement due to longer-range secondary electrons. Again, with NPs selectively internalised, the local effectiveness of MRT is expected to increase in the tumour. Dose enhancement produced by the shell aggregate varied more significantly in the cell population, depending on its location, when compared to a homogeneous NP distribution. These combined simulation and experimental data provide first evidence for optimising MRT through the incorporation of newly observed Ta2O5NP distributions within 9L cancer cells.
authors.affiliation: Centre for Medical Radiation Physics (CMRP), University of Wollongong, NSW, Australia.
authors.forename: Elette
authors.initials: E
authors.lastname: Engels
authors.affiliation: Centre for Medical Radiation Physics (CMRP), University of Wollongong, NSW, Australia; Radiation Oncology Department, Prince of Wales Hospital, Randwick, NSW, Australia.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Corde
authors.affiliation: Centre for Medical Radiation Physics (CMRP), University of Wollongong, NSW, Australia.
authors.forename: Sally
authors.initials: S
authors.lastname: McKinnon
authors.affiliation: CNRS/IN2P3, Centre d'Etudes Nucléaires de Bordeaux-Gradignan, UMR-5797, chemin du solarium, 33175 Gradignan, France; Université Bordeaux, Centre d'Etudes Nucléaires de Bordeaux-Gradignan, UMR-5797, chemin du solarium, 33175 Gradignan, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Incerti
authors.affiliation: Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, NSW, Australia; Institute for Superconducting and Electronic Materials (ISEM), University of Wollongong, NSW, Australia.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Konstantinov
authors.affiliation: Centre for Medical Radiation Physics (CMRP), University of Wollongong, NSW, Australia; Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, NSW, Australia.
authors.forename: Anatoly
authors.initials: A
authors.lastname: Rosenfeld
authors.affiliation: Centre for Medical Radiation Physics (CMRP), University of Wollongong, NSW, Australia; Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, NSW, Australia; Centre for Medical and Molecular Bioscience (CMMB), University of Wollongong, NSW, Australia.
authors.forename: Moeava
authors.initials: M
authors.lastname: Tehei
authors.affiliation: Centre for Medical Radiation Physics (CMRP), University of Wollongong, NSW, Australia; Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, NSW, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Lerch
authors.affiliation: Centre for Medical Radiation Physics (CMRP), University of Wollongong, NSW, Australia; Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, NSW, Australia. Electronic address: susanna@uow.edu.au.
authors.forename: Susanna
authors.initials: S
authors.lastname: Guatelli
mesh_terms: D001932:Brain Neoplasms / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D018316:Gliosarcoma / Q000532:radiotherapy; D006801:Humans; D055616:Microtechnology / Q000295:instrumentation*; D009010:Monte Carlo Method; D053758:Nanoparticles; D010087:Oxides / Q000737:chemistry* / Q000494:pharmacology*; D011829:Radiation Dosage; D011838:Radiation-Sensitizing Agents / Q000737:chemistry / Q000494:pharmacology; D011878:Radiotherapy / Q000295:instrumentation*; D011879:Radiotherapy Dosage; D017356:Synchrotrons; D013635:Tantalum / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D010087:Oxides; D011838:Radiation-Sensitizing Agents; D013635:Tantalum; C078151:tantalum oxide
keywords: Dose enhancement; Geant4; Microbeam radiation therapy; Nanoparticle