TY  - JOUR
A1  - Kempf, Harald
A1  - Bleicher, Marcus
A1  - Meyer-Hermann, Michael
T1  - Spatio-temporal dynamics of hypoxia during radiotherapy
T2  - PLoS One
N2  - 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.
Y1  - 2015
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/39045
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-390451
SN  - 1932-6203
N1  - Copyright: © 2015 Kempf et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
VL  - 10
IS  - (8): e0133357
SP  - 1
EP  - 23
PB  - PLoS
CY  - Lawrence, Kan.
ER  -