Selective, high-contrast detection of syngeneic glioblastoma in vivo

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dc.contributor.authorBanati, RBen_AU
dc.contributor.authorWilcox, Pen_AU
dc.contributor.authorXu, Ren_AU
dc.contributor.authorYin, Gen_AU
dc.contributor.authorSi, Een_AU
dc.contributor.authorSon, ETen_AU
dc.contributor.authorShimizu, Men_AU
dc.contributor.authorHolsinger, RMDen_AU
dc.contributor.authorParmar, Aen_AU
dc.contributor.authorZahra, Den_AU
dc.contributor.authorArthur, Aen_AU
dc.contributor.authorMiddleton, RJen_AU
dc.contributor.authorLiu, GJen_AU
dc.contributor.authorCharil, Aen_AU
dc.contributor.authorGraeber, MBen_AU
dc.date.accessioned2022-08-29T01:34:38Zen_AU
dc.date.available2022-08-29T01:34:38Zen_AU
dc.date.issued2020-06-19en_AU
dc.date.statistics2022-08-02en_AU
dc.descriptionOpen Access - This article is licensed under a Creative Commons Attribution 4.0 International License. An author correction was published here: https://doi.org/10.1038/s41598-020-72364-1. This article has been updated to reflect the correction. The correction is attached to this entry.en_AU
dc.description.abstractGlioblastoma is a highly malignant, largely therapy-resistant brain tumour. Deep infiltration of brain tissue by neoplastic cells represents the key problem of diffuse glioma. Much current research focuses on the molecular makeup of the visible tumour mass rather than the cellular interactions in the surrounding brain tissue infiltrated by the invasive glioma cells that cause the tumour’s ultimately lethal outcome. Diagnostic neuroimaging that enables the direct in vivo observation of the tumour infiltration zone and the local host tissue responses at a preclinical stage are important for the development of more effective glioma treatments. Here, we report an animal model that allows high-contrast imaging of wild-type glioma cells by positron emission tomography (PET) using [18 F]PBR111, a selective radioligand for the mitochondrial 18 kDa Translocator Protein (TSPO), in the Tspo−/− mouse strain (C57BL/6-Tspotm1GuMu(GuwiyangWurra)). The high selectivity of [18 F]PBR111 for the TSPO combined with the exclusive expression of TSPO in glioma cells infiltrating into null-background host tissue free of any TSPO expression, makes it possible, for the first time, to unequivocally and with uniquely high biological contrast identify peri-tumoral glioma cell invasion at preclinical stages in vivo. Comparison of the in vivo imaging signal from wild-type glioma cells in a null background with the signal in a wild-type host tissue, where the tumour induces the expected TSPO expression in the host’s glial cells, illustrates the substantial extent of the peritumoral host response to the growing tumour. The syngeneic tumour (TSPO+/+) in null background (TSPO−/−) model is thus well suited to study the interaction of the tumour front with the peri-tumoral tissue, and the experimental evaluation of new therapeutic approaches targeting the invasive behaviour of glioblastoma. © 2020, The Author(s).en_AU
dc.description.sponsorshipThis work was partially funded by the Australian Institute of Nuclear Science and Engineering (AINSE), Research Project ALNGRA14524, and Cure for Life Foundation/Cure Brain Cancer Australia.en_AU
dc.identifier.citationBanati, R. B., Wilcox, P., Xu, R., Yin, G., Si, E., Son, E. T., Shimizu, M., Holsinger, R. M. D., Parmar, A., Zahra, D., Arthur, A., Liu, G.-J., Charil, A. & Graeber, M. B. (2020). Selective, high-contrast detection of syngeneic glioblastoma in vivo. Scientific Reports, 10(1), 1-7. doi:10.1038/s41598-020-67036-zen_AU
dc.identifier.issn2045-2322en_AU
dc.identifier.issue1en_AU
dc.identifier.journaltitleScientific Reportsen_AU
dc.identifier.pagination1-7en_AU
dc.identifier.urihttps://doi.org/10.1038/s41598-020-67036-zen_AU
dc.identifier.urihttps://apo.ansto.gov.au/dspace/handle/10238/13637en_AU
dc.identifier.volume10en_AU
dc.language.isoenen_AU
dc.publisherSpringer Natureen_AU
dc.subjectAnimal cellsen_AU
dc.subjectGliomasen_AU
dc.subjectIn vivoen_AU
dc.subjectDrugsen_AU
dc.subjectNeoplasmsen_AU
dc.subjectBrainen_AU
dc.subjectNeurologyen_AU
dc.titleSelective, high-contrast detection of syngeneic glioblastoma in vivoen_AU
dc.typeJournal Articleen_AU
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