Optimizing dose enhancement with TaO nanoparticles for synchrotron microbeam activated radiation therapy.

Elette Engels, Stéphanie Corde, Sally McKinnon, Sébastien Incerti, Konstantin Konstantinov, Anatoly Rosenfeld, Moeava Tehei, Michael Lerch, Susanna Guatelli

Journal: Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB) 2017;32(12):1852-1861

PMID: 27866898

Full Text on Elsevier Science View on PubMed

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 TaO nanoparticles (NPs) in 9L gliosarcoma treated with MRT at the Australian Synchrotron, increased the treatment efficiency. TaO NPs 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 TaO NPs 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 TaO NP distributions within 9L cancer cells.

Address: Centre for Medical Radiation Physics (CMRP), University of Wollongong, NSW, Australia.; Centre for Medical Radiation Physics (CMRP), University of Wollongong, NSW, Australia; Radiation Oncology Department, Prince of Wales Hospital, Randwick, NSW, Australia.; 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.; Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, NSW, Australia; Institute for Superconducting and Electronic Materials (ISEM), University of Wollongong, NSW, Australia.; 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 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.; 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: [email protected].

DOI: 10.1016/j.ejmp.2016.10.024

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MeSH Terms: Brain Neoplasms, Cell Line, Tumor, Cell Survival, Gliosarcoma, Humans, Microtechnology, Monte Carlo Method, Nanoparticles, Oxides, Radiation Dosage, Radiation-Sensitizing Agents, Radiotherapy, Radiotherapy Dosage, Synchrotrons, Tantalum