) There is a need for new approaches to metabolic imaging of prostate and renal cancer. Positron emission tomography (PET) allows for cross sectional metabolic imaging, and is now emerging as an important clinical diagnostic imaging modality. PET imaging of glycolytic metabolism using the tracer fluorodeoxyglucose has proven useful in the diagnosis and staging of several malignancies, but has shown limited value in renal and prostate cancer. Positron radiotracers depicting metabolic pathways other than glycolytic metabolism are needed to fully develop the potential of PET in oncology. Carbon-11 acetate is a potential radiotracer for the depiction of the altered intermediary metabolism in malignant neoplasms. The purpose of this research is to understand the participating metabolic pathways responsible for the high uptake and retention of acetate radiotracer observed on PET imaging in certain malignant neoplasms, most notably renal cell carcinoma and prostate cancer. Acetate is a central molecule of intermediary metabolism with access to both catabolic and anabolic pathways. In this proposed research, the participating metabolic pathways and intermediate pools of acetate radiotracer will be investigated in vitro using cell culture and animal models of selected malignant neoplasms and tissue culture of pools will be correlated with measurements of the expression of enzymes involved in intermediary and anabolic lipid metabolism of acetate to understand the rate limiting steps and dominant tracer pools responsible for the uptake and retention of radiotracer acetate in certain malignancies. Kinetics of carbon-11 acetate on PET imaging of human subjects with prostate cancer and renal cancer prior to resection, and on micro PET imaging of athymic mice bearing xenographs of selected malignancies will be analyzed and compared to enzyme measurement of these tissues in vitro to determine the role of transport and intermediary metabolism enzyme expression in the tracer kinetics of renal and prostate cancer. The carbon-11 acetate imaging of human subjects with prostate cancer and renal cell carcinoma involved in this study will also be compared with surgical and histopathological findings to assess diagnostic accuracy in clinical diagnosis.
