Oncology:1 The efficacy of Fludeoxyglucose F 18 Injection in positron emission tomography cancer imaging was demonstrated in 16 independent literature reports. These studies prospectively evaluated the sensitivity and specificity of Fludeoxyglucose F 18 for detecting malignancies. All these studies had at least 50 patients and used pathology as a standard of truth to compare the results of PET imaging with Fludeoxyglucose F 18 Injection. The studies encompassed a variety of cancers: non-small cell lung cancer, colo-rectal, pancreatic, breast, thyroid, melanoma, Hodgkin’s and non-Hodgkin’s lymphoma, and various types of metastatic cancers to lung, liver, bone, and axillary nodes. The doses in the studies ranged from 200 MBq to 740 MBq with a median and mean dose of 370 MBq.

In these studies the patients had a clinical reason for the evaluation of malignancy (e.g., the patients had an abnormality identified by a prior test and were seeking a diagnosis, or the patients 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.