Long, Tong; (2019) Development of a 3D cancer model for MRI and radiobiology studies. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The biological experiments are often carried out in two-dimensional monolayer cultures. However, two-dimensional cell models are reported can not accurately reflect the three-dimensional in vivo tumour microenvironment such as oxygen gradient, nutrient supply. Then I further develop and establish a three-dimensional collagen based in vitro cancer model from our group research. The novelty includes the three-dimensional cancer spheroid model developments and development of high collagen density three-dimensional cancer models. Types of colorectal cancer cell lines are used to build the three-dimensional cancer models and the biological properties such as metabolism and cell invasion are characterized. The development of three-dimensional cancer model is also applied on MRI session to explore the relationship between MR imaging contrast, collagen density and cell density. This includes sample design, the T1 and T2 imaging sequence parameter optimization and data analysis. The three-dimensional cancer model is also applied in radiobiology studies. The cancer models are either proton and photon irradiated, followed by immunofluorescent staining and imaging. Cell apoptosis marker, DNA double strand break marker and hypoxia marker are used to analyze the biological changes after irradiation.

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