ee decay factors in table 3. patient preparation : blood glucose levels should be stabilized before fludeoxyglucose f 18 injection is administered. in non-diabetic patients this may be accomplished by fasting 4-6 hours before fludeoxyglucose f 18 injection. diabetic patients may need stabilization of blood glucose on the day preceding and on the day of administration of fludeoxyglucose f 18 injection. for cardiac imaging, administration of fludeoxyglucose f 18 injection to fasting patients limits the accumulation of fludeoxyglucose f 18 to ischemic myocardium. this may make localization of the ischemic region difficult because the surrounding myocardium will not be well visualized. conversely, administration of fludeoxyglucose f 18 injection to patients who have received a glucose load (e.g., 50-75 grams, 1-2 hours before administration of fludeoxyglucose f 18 injection) allows the surrounding, non-ischemic myocardium to be seen and facilitates localization of ischemic areas. imaging: optimally, it is recommended that positron emission tomography (pet) imaging be initiated within 40 minutes of administration of fludeoxyglucose f 18 injection. static emission scans are acquired 30-100 minutes from time of injection.

ound activity of the specific organ or tissue type, regions of decreased or absent uptake of fludeoxyglucose f 18 reflect the decrease or absence of glucose metabolism. regions of increased uptake of fludeoxyglucose f 18 reflect greater than normal rates of glucose metabolism. pharmacodynamics fludeoxyglucose f 18 injection is rapidly distributed to all organs of the body after intravenous administration. after background clearance of fludeoxyglucose f 18 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 the 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 f 18 accumulation shows considerable variability. depending on tumor type, stage, and location, fludeoxyglucose f 18 accumulation may be increased, normal, or decreased. also, inflammatory cells can have the same variability of uptake of fludeoxyglucose f 18. 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 stimulated, and glucose taken up by the myocyte is metabolized immediately instead of being converted into glycogen. under these conditions, phosphorylated fludeoxyglucose f 18 accumulates in the myocyte and can be detected with pet imaging. normally, the brain relies on anaerobic metabolism. in epilepsy, the glucose metabolism varies. generally, during a seizure, glucose metabolism increases. interictally, the seizure focus tends to be hypometabolic. pharm a c okinetics in four healthy male volunteers, receiving an intravenous administration of 30 seconds in duration, the arterial blood level profile for fludeoxyglucose f 18 was described as a triexponential decay curve. 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 11.6 ± 1.1 min, and 80-95 minutes with a mean and std of 88 ±□ 4 min. plasma protein binding the extent of binding of fludeoxyglucose f 18 to plasma proteins is not known. metabolism fludeoxyglucose f 18 is transported into cells and phosphorylated to [ 18 f]-fdg-6-phosphate at a rate proportional to the rate of glucose utilization within that tissue. [ 18 f]-fdg-6-phosphate presumably is metabolized to 2-deoxy-2-[ 18 f]fluoro-6-phospho-d-mannose ([ 18 f]fdm-6-phosphate). fludeoxyglucose f 18 injection may contain several impurities (e.g., 2-deoxy-2-chloro-d-glucose (cldg)). biodistribution and metabolism of c1dg are presumed to be similar to fludeoxyglucose f 18 and would be expected to result in intracellular formation of 2-deoxy-2-chloro-6-phospho-d-glucose (c1dg-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, c1dg, and cldm) presumably leave cells by passive diffusion. fludeoxyglucose f 18 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 f 18 that is not involved in glucose metabolism in any tissue is then excreted in the urine. excretion fludeoxyglucose f 18 is cleared from most tissues within 24 hours and can be eliminated from the body unchanged in the urine. three elimination phases have been identified in the reviewed literature. 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. pharmacokinetics in special populations extensive dose range and dose adjustment studies with this drug product in normal and special populations have not been completed. in pediatric patients with epilepsy, doses given have been as low as 2.6 mci. the pharmacokinetics of fludeoxyglucose f 18 injection in renally-impaired patients have not been characterized. fludeoxyglucose f 18 is eliminated through the renal system. care should be taken to prevent excessive and unnecessary 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 f 18 distribution in humans have not been ascertained. diabetic patients may need stabilization of blood glucose levels on the day before and on the day of the fludeoxyglucose f 18 injection study. drug-drug interactions drug-drug interactions with fludeoxyglucose f 18 injection have not been evaluated.

atients had an existing diagnosis of cancer and were having further work-up or monitoring). none of these studies evaluated the use of fludeoxyglucose f 18 injection in routine population screening in which healthy, asymptomatic people are tested for purposes of cancer early detection. the efficacy of fludeoxyglucose f 18 pet imaging in cancer screening, including its ability to decrease cause-specific mortality, is unknown. in pet imaging with fludeoxyglucose f 18 injection, sensitivity is restricted by the biologic variability of cancer glucose utilization found in individual patients, with different cancers (see clinical pharmacology and pharmacodynamic sections). in the reviewed studies, the sensitivity and specificity varied with the type of cancer, size of cancer, and other clinical parameters. also, there were false negatives and false positives. negative pet imaging results with fludeoxyglucose f 18 injection do not preclude the diagnosis of cancer and further work-up is indicated. also, positive pet imaging results with fludeoxyglucose f 18 injection cannot replace biopsy to confirm a diagnosis of cancer. there are non-malignant conditions such as fungal infections, inflammatory processes, and benign tumors that had patterns of increased glucose metabolism that give rise to false-positive examinations. cardiology: 2 the efficacy of fludeoxyglucose f 18 injection for cardiac use was demonstrated in ten independent literature reports, which, in general, shared the characteristics summarized below. the studies were prospective and enrolled patients with coronary artery disease and chronic left ventricular systolic dysfunction of a mild to moderate degree. the patients were scheduled to undergo coronary revascularization with either coronary artery bypass surgery or angioplasty. before revascularization, patients underwent pet imaging with fludeoxyglucose f 18 injection and perfusion imaging with other diagnostic radiopharmaceuticals. doses of fludeoxyglucose f 18 injection ranged from 74-370 mbq (2-10 mci). segmental, left ventricular, wall-motion assessments of asynergic areas made before revascularization were compared to those made after successful revascularization to identify myocardial segments with functional recovery. segmental wall motion assessments were made blinded to the results of metabolic/perfusion imaging, and pet image analyses were quantitative. left ventricular myocardial segments were predicted to have reversible loss of systolic function if they showed fludeoxyglucose f 18 accumulation and reduced perfusion (i.e., flow-metabolism mismatch). conversely, myocardial segments were predicted to have irreversible loss of systolic function if they showed concordant reductions in both fludeoxyglucose f 18 accumulation and perfusion (i.e., matched defects). diagnostic performance measures such as sensitivity, specificity, positive predictive value, and negative predictive value were calculated. none of the studies prospectively determined the degree to which mismatch, or the location of mismatch, is associated with improvements in global ventricular function, clinical symptoms, exercise tolerance, or survival. findings of flow-metabolism mismatch in a myocardial segment suggest that successful revascularization will restore myocardial function in that segment. however, false-positive tests occur regularly, and the decision to have a patient undergo revascularization should not be based on pet findings alone. similarly, findings of a matched defect in a myocardial segment suggest that myocardial function will not recover in that segment, even if it is successfully revascularized. however, false-negative tests occur regularly, and the decision to recommend against coronary revascularization, or to recommend a cardiac transplant, should not be based on pet findings alone. the reversibility of segmental dysfunction as predicted with fludeoxyglucose f 18 pet imaging depends on successful coronary revascularization. therefore, in patients with a low likelihood of successful revascularization, the diagnostic usefulness of pet imaging with fludeoxyglucose f 18 injection is limited. epilepsy: 3 in a prospective, open label trial, fludeoxyglucose f 18 injection was evaluated in 86 patients with epilepsy. each patient received a dose of fludeoxyglucose f 18 injection in the range of 185-370 mbq (5-10 mci). demographic characteristics of race and gender are 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 complex 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-fludeoxyglucose f 18 injection findings were confirmed by fludeoxyglucose f 18; 34% (30/87) of patients, images of fludeoxyglucose f 18 injection provided new findings. in 32% (27/87), imaging with fludeoxyglucose f 18 injection was not definitive. the influence of these findings on surgical outcome, medical management, or behavior is not known. several other studies comparing imaging with fludeoxyglucose f 18 injection results to subsphenoidal eeg, mri and/or surgical findings supported the concept that the degree of hypometabolism corresponds to areas of confirmed epileptogenic foci. the safety and effectiveness of fludeoxyglucose f 18 injection to distinguish idiopathic epileptogenic foci from tumors or other brain lesions that may cause seizures have not been established.