Fdg Pharmacology, Pharmacokinetics, Studies, Metabolism - Fluorodeoxyglucose F18 Inj

Fdg Pharmacology, Pharmacokinetics, Studies, Metabolism - Fluorodeoxyglucose F18 Inj

CLINICAL PHARMACOLOGY

General

[18F]FDG, a radiolabeled analog of glucose, rapidly distributes, after intravenous injection, to all organs of the body. After background clearance, peak imaging is at 30 - 40 minutes after injection.

Table 3. Physical Decay Chart for Fluorine F 18

Pharmacokinetics

In 4 normal male volunteers, after an intravenous dose given over 30 seconds, the arterial blood level profile for [18F]FDG can be described by a triexponential decay curve. The half-lives for the different distribution and elimination phases are 0.2-0.3 min, 10-13 min (mean ± s.d.; 11.6 ± 1.1 min), and 80-95 min (88 ± 4 min).

Within 33 minutes, a mean of 3.9% of the injected dose can be measured in the urine. Bladder activity two hours after injection indicates that a mean of 20.6% of the injected dose is present. See the Metabolism Section for additional clearance times.

Metabolism

[18F]FDG is taken up by cells and phosphorylated to [18F]FDG-6-phosphate at a rate proportional to the rate of glucose utilization within a given tissue. [18F]FDG-6-phosphate presumably is metabolized to 2-deoxy-2-[18F]fluoro-6-phospho- D -mannose [18F]FDM-6-phosphate).

[18F]FDG contains 2-deoxy-2-chloro- D -glucose (ClDG) as an impurity. Distribution and metabolism of ClDG are presumably similar to that of [18F]FDG, 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.

FDG and related compounds are cleared from non-cardiac tissues within 3 to 24 hours after administration; clearance from the heart may require more than 96 hours. [18F]FDG that is not involved in glucose metabolism is excreted unchanged in the urine.

Pharmacodynamics
[18F]FDG is a glucose analogue which concentrates in cells that rely upon glucose as a primary energy source. Once in the cell it is phosphorylated and can not exit until dephosphorylation has occurred. Regions of "increased [18F]FDG uptake" correlate with increased glucose metabolism. Regions of decreased/absent uptake reflect the absence of glucose metabolism. Background activity reflects uptake by normal cells. [18F]FDG uptake in inflammatory cells is inconsistent and may be increased, normal or decreased. Whether or not [18F]FDG, ClDG, or their metabolites can inhibit glucose metabolism is not known.

CLINICAL TRIALS

In a prospective, open label trial, [18F]FDG was evaluated in 86 patients with epilepsy. Each patient received a dose of [18F]FDG in the range of 185-370 MBq (5-10) mCi. Demographic characteristics of race and gender or not available. The mean age was 16.4 years (range: 4 months - 58 years; of these, 42 patients were <12 years and 16 patients were <2 years old). Patients had a known diagnosis of complete partial epilepsy and were under evaluation as surgical candidates for treatment of their seizure disorder. Seizure foci had been previously identified on ictal EEGs and sphenoidal EEGs. In 16% (14/87) of patients, the pre-[18F]FDG findings were confirmed by [18F]FDG; 34% (30/87) of patients, FDG scans provided new findings. In 32% (27/87), FDG scans were not definitive. The influence of these findings on surgical outcome, medical management or behavior is not known.

In several other studies comparing [18F]FDG scan results to subsphenoidal EEG, MRI and/or surgical findings, the degree of hypometabolism corresponded to areas of confirmed epileptogenic foci.