FDG- PET Imaging in Neurodegenerative Brain Diseases

Increases and decreases of synaptic activity in the brain are accompanied by proportional changes in capillary perfusion and local glucose consumption. These changes in glucose consumption are the effect of changed activity or density of the afferent nerve terminals in that region. Loss of neurons may result in decreased glucose consumption in distant brain regions by deafferentiation, while also increased regional glucose consumption by increased activation of afferent neurons can occur. The PET tracer [18F]fluorodeoxyglucose (FDG) allows the measurement of glucose consumption. FDG is a glucose analog with physiological aspects almost identical to glucose. It is transported from the blood to the brain by a carrier-mediated diffusion mechanism. FDG and glucose are phosphorylated by hexokinase as the first step of the glycolytic process. FDG differs from glucose in that a hydrogen atom replaced the hydroxyl group at the second carbon atom of the molecule. Glucose is then phosphorylated to glucose-6PO4, and continues along the glycolytic pathway for energy production. However, FDG is phosphorylated to FDG-6-PO4, which is not a substrate for further metabolism and trapped in tissues. As glucose is the only source of energy for the brain it reflects the neuronal integrity of underlying brain pathology. Since FDG is a competitive substrate with glucose for both transport and phosphorylation, it is important for tracer uptake to avoid high blood glucose levels during an FDG-PET scan in subjects with diabetes.