[11C]Acetoacetate

Excerpt

Acetate is readily taken up by cells and is activated to acetyl-CoA in both the cytosol and mitochondria by acetyl-CoA synthetase. Acetyl-CoA is a common metabolic intermediate for synthesis of cholesterol and fatty acids, which are then incorporated into membrane tissue (1). Acetyl-CoA is oxidized in mitochondria by the tricarboxylic acid (TCA) cycle to carbon dioxide and water. Some of the acetate is converted to amino acids. In normal myocardium, acetate is metabolized to CO₂via the TCA cycle as the dominant pathway. In contrast, tumor cells convert most of the acetate into fatty acids by a key enzyme fatty acid synthetase, which is overexpressed in cancer cells (2). Acetate is predominantly incorporated into intracellular phosphatidylcholine membrane microdomains that are important for tumor growth and metastasis (3). [¹¹C]Acetate is used as a positron emission tomography (PET) tracer in the study of myocardial oxidative metabolism and regional myocardial blood flow (4). [¹¹C]Acetate is a promising PET tracer for renal, pancreatic, and prostate tumors (5).

Under normal conditions, glucose is converted to acetate to feed into the TCA cycle for energy generation. However, ketone bodies (acetoacetate and hydroxybutyrate) are produced by the liver when the carbohydrate intake is low or during fasting. Liver cells do not utilize the ketone bodies because of a lack of acetoacetyl-CoA transferase for the metabolism of acetoacetate. The ketone bodies became the primary source of energy for the brain, heart, kidney, and skeletal muscle, where they are converted to acetyl-CoA. Human mammary carcinomas and rat hepatomas were found to express increased levels of acetoacetyl-CoA transferase activity in correlation with their growth rates (6, 7). [¹¹C]Acetoacetate ([¹¹C]ACAC ) is being evaluated as a PET agent to measure ketone body utilization by the tumors and brain (8, 9).