Pakzad, F.; (2010) Molecular imaging using positron emission tomography in gastrointestinal malignancy. Doctoral thesis , UCL (University College London).

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Abstract

Positron Emission Tomography (PET) with 18F-FDG has emerged as a powerful tool in oncology. Furthermore, recent advent of PET/CT and novel tracers are continually expanding its role. This thesis investigates its application in two solid cancer models. In the diagnosing of primary pancreatic cancer, 18F-FDG PET/CT was shown to be more accurate than conventional CT. It did not add information to locoregional staging of disease but impacted management of patients with potentially operable tumours, by accurately confirming the presence / absence of metastases. In the pre-operative staging of patients with colorectal liver metastases (CLM), 18F- FDG PET/CT was also superior to CT in assessing extrahepatic disease, where it again impacted management. The accuracy of detecting hepatic disease was similar for both. Compared to PET alone, PET/CT improved the accuracy of lesions localization and interpretation. Next, the feasibility of imaging with the novel thymidine analogue tracer 18F-FLT was investigated. Overall, 18F-FLT PET was less accurate than 18F-FDG in detecting lesions in both cancer types, thus suggesting it to be an unsuitable tracer for routine diagnosis and staging. In the cohort of pancreatic cancer patients, 18F-FLT uptake (SUVs) were found to strongly correlate with the immunohistochemical proliferation marker, Ki-67 antigen. This supported 18F-FLT‟s potential role as a surrogate marker of proliferation. The prognostic implications of these require further investigation. Finally, an in vitro model was use to examine early changes in 18F-FLT uptake in response to treatment with cytotoxics. At 2 hours following pulse treatment with 5-fluorouracil, (and before changes in cell numbers and cell cycle phase were seen), a dose dependent increase in 18F-FLT uptake was seen. No change was observed with 18F-FDG nor following Cisplatin treatment. This adaptive response may have a role as an early predictor of response to 5-FU (and potentially other antimetabolites), which requires further investigation.

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