2.50
Hdl Handle:
http://hdl.handle.net/10033/610436
Title:
Spatio-Temporal Dynamics of Hypoxia during Radiotherapy.
Authors:
Kempf, Harald; Bleicher, Marcus; Meyer-Hermann, Michael ( 0000-0002-4300-2474 )
Abstract:
Tumour hypoxia plays a pivotal role in cancer therapy for most therapeutic approaches from radiotherapy to immunotherapy. The detailed and accurate knowledge of the oxygen distribution in a tumour is necessary in order to determine the right treatment strategy. Still, due to the limited spatial and temporal resolution of imaging methods as well as lacking fundamental understanding of internal oxygenation dynamics in tumours, the precise oxygen distribution map is rarely available for treatment planing. We employ an agent-based in silico tumour spheroid model in order to study the complex, localized and fast oxygen dynamics in tumour micro-regions which are induced by radiotherapy. A lattice-free, 3D, agent-based approach for cell representation is coupled with a high-resolution diffusion solver that includes a tissue density-dependent diffusion coefficient. This allows us to assess the space- and time-resolved reoxygenation response of a small subvolume of tumour tissue in response to radiotherapy. In response to irradiation the tumour nodule exhibits characteristic reoxygenation and re-depletion dynamics which we resolve with high spatio-temporal resolution. The reoxygenation follows specific timings, which should be respected in treatment in order to maximise the use of the oxygen enhancement effects. Oxygen dynamics within the tumour create windows of opportunity for the use of adjuvant chemotherapeutica and hypoxia-activated drugs. Overall, we show that by using modelling it is possible to follow the oxygenation dynamics beyond common resolution limits and predict beneficial strategies for therapy and in vitro verification. Models of cell cycle and oxygen dynamics in tumours should in the future be combined with imaging techniques, to allow for a systematic experimental study of possible improved schedules and to ultimately extend the reach of oxygenation monitoring available in clinical treatment.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Spatio-Temporal Dynamics of Hypoxia during Radiotherapy. 2015, 10 (8):e0133357 PLoS ONE
Journal:
PloS one
Issue Date:
2015
URI:
http://hdl.handle.net/10033/610436
DOI:
10.1371/journal.pone.0133357
PubMed ID:
26273841
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the research group system immunology ([BRICS]SIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorKempf, Haralden
dc.contributor.authorBleicher, Marcusen
dc.contributor.authorMeyer-Hermann, Michaelen
dc.date.accessioned2016-05-20T11:41:31Zen
dc.date.available2016-05-20T11:41:31Zen
dc.date.issued2015en
dc.identifier.citationSpatio-Temporal Dynamics of Hypoxia during Radiotherapy. 2015, 10 (8):e0133357 PLoS ONEen
dc.identifier.issn1932-6203en
dc.identifier.pmid26273841en
dc.identifier.doi10.1371/journal.pone.0133357en
dc.identifier.urihttp://hdl.handle.net/10033/610436en
dc.description.abstractTumour hypoxia plays a pivotal role in cancer therapy for most therapeutic approaches from radiotherapy to immunotherapy. The detailed and accurate knowledge of the oxygen distribution in a tumour is necessary in order to determine the right treatment strategy. Still, due to the limited spatial and temporal resolution of imaging methods as well as lacking fundamental understanding of internal oxygenation dynamics in tumours, the precise oxygen distribution map is rarely available for treatment planing. We employ an agent-based in silico tumour spheroid model in order to study the complex, localized and fast oxygen dynamics in tumour micro-regions which are induced by radiotherapy. A lattice-free, 3D, agent-based approach for cell representation is coupled with a high-resolution diffusion solver that includes a tissue density-dependent diffusion coefficient. This allows us to assess the space- and time-resolved reoxygenation response of a small subvolume of tumour tissue in response to radiotherapy. In response to irradiation the tumour nodule exhibits characteristic reoxygenation and re-depletion dynamics which we resolve with high spatio-temporal resolution. The reoxygenation follows specific timings, which should be respected in treatment in order to maximise the use of the oxygen enhancement effects. Oxygen dynamics within the tumour create windows of opportunity for the use of adjuvant chemotherapeutica and hypoxia-activated drugs. Overall, we show that by using modelling it is possible to follow the oxygenation dynamics beyond common resolution limits and predict beneficial strategies for therapy and in vitro verification. Models of cell cycle and oxygen dynamics in tumours should in the future be combined with imaging techniques, to allow for a systematic experimental study of possible improved schedules and to ultimately extend the reach of oxygenation monitoring available in clinical treatment.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshCell Hypoxiaen
dc.subject.meshCell Line, Tumoren
dc.subject.meshModels, Theoreticalen
dc.subject.meshRadiotherapyen
dc.titleSpatio-Temporal Dynamics of Hypoxia during Radiotherapy.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalPloS oneen
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