PET-based analysis of tumor glucose metabolism and tumor hypoxia before and during anti-neoplastic treatment

Tumour hypoxia is an important contributor to chemo-radiotherapy resistance. This has been demonstrated in several tumour types including non-small cell lung cancer and head and neck squamous cell carcinoma. Tumour hypoxia is a dynamic process; some parts of the tumour exhibit higher levels of hypoxia than others due to differences in blood flow as a result of constantly changing tumour microenvironment. Therefore, precise delivery of higher radiation doses per fraction to the specific hypoxic sub-volumes of tumour identified by FAZA-PET imaging may improve the therapeutic ratio by increasing local tumour control without inducing excess radiation induced side effects. This requires identification of spatio-temporal dynamics of tumour hypoxia during treatment. In our study, we used FAZA-PET imaging to detect heterogeneous distribution of hypoxic sub-volumes out of homogeneous FDG background in a tumour. Most importantly, we observed relatively stable tumour hypoxia at FAZA-week 2 of chemoradiotherapy. Hence, FAZA-PET might be developed into a tool for guiding adaptive radiotherapy treatment planning. However, additional studies are needed on the spatial-temporal dynamics of tumour hypoxia, to stratify patients who may benefit from hypoxia based radiotherapy treatment planning before implementation.

Dissertation: http://irs.ub.rug.nl/ppn/387288074