Fludeoxyglucose (18F) - Mechanism of Action, Metabolic End-products, and Metabolic Rate

Mechanism of Action, Metabolic End-products, and Metabolic Rate

18F-FDG, as a glucose analog, is taken up by high-glucose-using cells such as brain, kidney, and cancer cells, where phosphorylation prevents the glucose from being released again from the cell, once it has been absorbed. The 2' hydroxyl group (—OH) in normal glucose is needed for further glycolysis (metabolism of glucose by splitting it), but 18F-FDG is missing this 2' hydroxyl. Thus, in common with its sister molecule 2-deoxy--glucose, FDG cannot be further metabolized in cells. The 18F-FDG-6-phosphate formed when 18F-FDG enters the cell thus cannot move out of the cell before radioactive decay. As a result, the distribution of 18F-FDG is a good reflection of the distribution of glucose uptake and phosphorylation by cells in the body.

After 18F-FDG decays radioactively, however, its 2'-fluorine is converted to 18O–, and after picking up a proton H+ from a hydronium ion in its aqueous environment, the molecule becomes glucose-6-phosphate labeled with harmless nonradioactive "heavy oxygen" in the hydroxyl at the 2' position. The new presence of a 2' hydroxyl now allows it to be metabolized normally in the same way as ordinary glucose, producing non-radioactive end-products.

Although in theory all 18F-FDG is metabolized as above with a radioactivity elimination half-life of 110 minutes (the same as that of fluorine-18), clinical studies have shown that the radioactivity of 18F-FDG partitions into two major fractions. About 75% of the fluorine-18 activity remains in tissues and is eliminated with a half-life of 110 minutes, presumably by decaying in place to O-18 to form 18O-glucose-6-phosphate, which is non-radioactive (this molecule can soon be metabolized to carbon dioxide and water, after nuclear transmutation of the fluorine to oxygen ceases to prevent metabolism). Another fraction of 18F-FDG, representing about 20% of the total fluorine-18 activity of an injection, is eliminated renally by two hours after a dose of 18F-FDG, with a rapid half-life of about 16 minutes (this portion makes the renal-collecting system and bladder prominent in a normal PET scan). This short biological half-life indicates that this 20% portion of the total fluorine-18 tracer activity is eliminated pharmacokinetically (through the renal system) much more quickly than the isotope itself can decay. The rapidity also suggests that some of this 18F is no longer attached to glucose, since low concentrations of glucose in the blood are retained by the normal kidney and not passed into the urine. Because of this rapidly excreted urine 18F, the urine of a patient undergoing a PET scan may therefore be especially radioactive for several hours after administration of the isotope.

All radioactivity of 18F-FDG, both the 20% which is rapidly excreted in the first several hours of urine which is made after the exam, and the 80% which remains in the patient, decays with a half-life of 110 minutes (just under 2 hours). Thus, within 24 hours (13 half-lives), the radioactivity in the patient and in any initially voided urine which may have contaminated bedding or objects after the PET exam, will have decayed to 2−13 = 1/8192 of the initial radioactivity of the dose.