FAZA PET as Biomarker for Hypoxia in Rectal Cancer

Colorectal cancer (CRC) is one of the leading causes of cancer mortality in Canada. Rectal cancers are now known to be hypoxic which is a negative prognostic factor and predictive of metastatic spread and poor responsiveness to treatment. This has also been shown in preclinical xenograft models. Hence there is a need for identification of hypoxic rectal cancers. In this pilot study the investigators intend to non-invasively assess the tumor and nodal metastasis using an integrated Positron Emission Tomography-Magnetic Resonance Imaging scanner (PET/MRI) with 18F-Fluoroazomycin Arabinoside (18F-FAZA) a radiopharmaceutical for assessing tumor hypoxia. The hypoxic rectal tumors will show an increased uptake of 18F-FAZA on PET which will have morphological correlation on MRI. The patient will then undergo neoadjuvant chemoradiation therapy (CRT) followed by repeat 18F-FAZA PET/MRI and rectal cancer surgery with pimonidazole staining. Pimonidazole is an extrinsic marker of hypoxia that is selectively reduced and covalently bound to intracellular macromolecules in areas of hypoxia within normal and tumor tissue with current approval for use in humans for research studies. The primary goal of this pilot trial is to validate FAZA-PET as a biomarker of hypoxia by correlating its uptake in rectal tumors to pimonidazole staining in histopathology specimens. If the investigators pilot study successfully demonstrates the uptake and correlation of pimonidazole and FAZA-PET, the investigators would like to initiate a larger study examining hypoxia in rectal cancer. The investigators aims would be to image patients with locally advanced rectal cancer before CRT to ascertain whether high FAZA-PET uptake correlates with poor outcome to CRT. The ability to preoperatively predict the patient sub-population that will respond best to CRT, will help to identify the "complete pathological" responders and avoid unnecessary surgery. Furthermore, the FAZA-PET high subset of patients may ben