Fludeoxyglucose ¹⁸F Other names: Fludeoxyglucose (18F)

F18 Fludeoxyglucose is a glucose analog that concentrates in cells that rely upon glucose as an energy source, or in cells whose dependence on glucose increases under pathophysiological conditions. Fludeoxyglucose F18 is transported through the cell membrane by facilitative glucose transporter proteins and is phosphorylated within the cell to [F18]-FDG-6-phosphate by the enzyme hexokinase. Once phosphorylated it cannot exit until it is dephosphorylated by glucose-6-phosphatase. Therefore, within a given tissue or pathophysiological process, the retention and clearance of fludeoxyglucose F18 reflect a balance involving glucose transporter, hexokinase and glucose-6-phosphatase activities. Fludeoxyglucose F18 is used to assess glucose metabolism.

In comparison to background activity of the specific organ or tissue type, regions of decreased or absent uptake of fludeoxyglucose F18 reflect the decrease or absence of glucose metabolism. Regions of increased uptake of fludeoxyglucose F18 reflect greater than normal rates of glucose metabolism.

Fludeoxyglucose F18 injection is rapidly distributed to all organs of the body after intravenous administration. After background clearance of fludeoxyglucose F18 injection, optimal PET imaging is generally achieved between 30 to 40 minutes after administration.

In cancer, the cells are generally characterized by enhanced glucose metabolism partially due to (1) an increase in activity of glucose transporters, (2) an increased rate of phosphorylation activity, (3) a reduction of phosphatase activity or, (4) a dynamic alteration in the balance among all these processes. However, glucose metabolism of cancer as reflected by fludeoxyglucose F18 accumulation shows considerable variability. Depending on tumor type, stage, and location, fludeoxyglucose F18 accumulation may be increased, normal, or decreased. Also, inflammatory cells can have the same variability of uptake of fludeoxyglucose F18.

In the heart, under normal aerobic conditions, the myocardium meets the bulk of its energy requirements by oxidizing free fatty acids. Most of the exogenous glucose taken up by the myocyte is converted into glycogen. However, under ischemic conditions, the oxidation of free fatty acids decreases, exogenous glucose becomes the preferred myocardial substrate, glycolysis is stimulated, and glucose taken up by the myocyte is metabolized immediately instead of being converted into glycogen. Under these conditions, phosphorylated fludeoxyglucose F18 accumulates in the myocyte and can be detected with PET imaging.

In the brain, cells normally rely on aerobic metabolism. In epilepsy, the glucose metabolism varies. Generally, during a seizure, glucose metabolism increases. Interictally, the seizure focus tends to be hypometabolic.

Distribution

In four healthy male volunteers, receiving an intravenous administration of 30 seconds in duration, the arterial blood level profile for fludeoxyglucose F18 decayed triexponentially. The effective half-life ranges of the three phases were 0.2-0.3 minutes, 10-13 minutes with a mean and standard deviation (STD) of 12 ± (1) min, and 80-95 minutes with a mean and STD of 88 ± (4) min.

Plasma protein binding of fludeoxyglucose F18 has not been studied.

Metabolism

Fludeoxyglucose F18 is transported into cells and phosphorylated to [F18]-FDG-6-phosphate at a rate proportional to the rate of glucose utilization within that tissue. [F18]-FDG-6-phosphate presumably is metabolized to 2-deoxy-2-[F18]fluoro-6-phospho-D-mannose([F18]FDM-6-phosphate).

Fludeoxyglucose F18 injection USP may contain several impurities (e.g., 2-deoxy-2-chloro-D-glucose (ClDG)). Biodistribution and metabolism of ClDG are presumed to be similar to fludeoxyglucose F18 and would be expected to result in intracellular formation of 2-deoxy-2-chloro-6-phospho-D-glucose (ClDG-6-phosphate) and 2-deoxy-2-chloro-6-phospho-D-mannose (ClDM-6-phosphate). The phosphorylated deoxyglucose compounds are dephosphorylated and the resulting compounds (FDG, FDM, ClDG, and ClDM) presumably leave cells by passive diffusion. Fludeoxyglucose F18 and related compounds are cleared from non-cardiac tissues within 3 to 24 hours after administration. Clearance from the cardiac tissue may require more than 96 hours. Fludeoxyglucose F18 that is not involved in glucose metabolism in any tissue is then excreted in the urine.

Elimination

Fludeoxyglucose F18 is cleared from most tissues within 24 hours and can be eliminated from the body unchanged in the urine. Within 33 minutes, a mean of 3.9% of the administrated radioactive dose was measured in the urine. The amount of radiation exposure of the urinary bladder at two hours post-administration suggests that 20.6% (mean) of the radioactive dose was present in the bladder.

Special Populations

The pharmacokinetics of fludeoxyglucose F18 injection have not been studied in renally-impaired, hepatically impaired or pediatric patients. Fludeoxyglucose F18 is eliminated through the renal system. Avoid excessive radiation exposure to this organ system and adjacent tissues.

The effects of fasting, varying blood sugar levels, conditions of glucose intolerance, and diabetes mellitus on fludeoxyglucose F18 distribution in humans have not been ascertained.