Although a majority of cancer patients will receive a course of radiation as part of their treatment, many of those patients will have a local recurrence of their cancer. Radiation therapy affects also the tumour microenvironment; however, its response, including the tumour vasculature is poorly understood. Tumour vasculature itself is generally not reported to be functionally damaged by doses of radiation below ~15Gy, but the status of surviving endothelial cells is still unknown. Our aim was to delineate the response of tumour blood vessels to radiation therapy and follow it in time.
We used a transgenic mouse model in which only endothelial cells express tdTomato after treatment with Tamoxifen. An abdominal window chamber was surgically implanted in mice and murine colon carcinoma MC38 GFP tumours induced. The developing tumour vasculature and perfusion was then imaged for up to 15 consecutive days with multiphoton intravital microscopy. We followed the response of tumour vasculature to single dose radiation (15 Gy) delivered by Small Animal Radiation Research Platform (SARRP) for up to 10 days after irradiation in the same tumour. Further, to assess and improve mathematical models of blood flow in tumour vasculature, we performed in vivo particle tracking of erythrocytes in tumour blood vessels in combination with measurements of flow in microfluidics channels.
Our transgenic mouse model in combination with longitudinal intravital imaging sets the stage for in vivo visual investigation of the development of tumour vasculature and its response to different treatments including radiation therapy.