Radiopharmaceutics & PET Radiochemistry MSc – Research Project Titles 1. Effect of COX-2 inhibition on choline uptake and metabolism in prostate cancer

Abnormal choline metabolism serves as a marker associated with oncogenesis and tumour progression. 11Cand 18F-labeled choline are positron emission tomography (PET) tracers used to study choline uptake. Nuclear magnetic resonance spectroscopy (NMRS) can detect choline and choline metabolites non-invasively; increased levels of these compounds serve as biomarkers of transformation, staging and response to therapy. Furthermore, enzymes of choline metabolism, such as choline kinase, present novel targets for image-guided cancer therapy. The arachidonic acid pathway plays a major role in the development and progression of a number of cancers, including prostate cancer. Epidemiological evidence suggests that nonsteroidal anti-inflammatory drugs may decrease the risk of prostate cancer, possibly through the inhibition of cyclooxygenase-2 (COX-2). Furthermore, COX-2 has been shown to regulate choline phospholipid metabolism, through effects on choline kinase expression, in breast cancer cells. However, studies have not been carried out on the effects of COX-2 on choline metabolism in prostate cancer cells. The project will use 11C (or 18F)-choline to study choline uptake, NMRS to study choline metabolism, and immunoblotting to determine expression of proteins involved in choline uptake and metabolism, in 3 prostate cancer cell lines: androgen-dependent LNCaP cells and androgen-resistant DU145 and PC3 cells which have low, moderate, and high metastatic potential, respectively. The aim of the proposed study is to determine if the degree of cancer aggressiveness correlates with choline uptake and/or metabolism, and if so, whether cancer aggressiveness is affected by COX-2 inhibition. All cell lines will be provided by Dr. Jonathan Morris (Cancer Studies, KCL). Key techniques learned/performed by student: Cell culture, NMR spectroscopy, immunoblotting, cellular PET tracer uptake Student description: This project would suit a biomedical student who may be interested in going on to a Ph.D.