INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Fludeoxyglucose F18 Injection is indicated for positron emission tomography (PET) imaging in the following settings: Fludeoxyglucose F18 Injection is indicated for positron emission tomography (PET) imaging in the following settings:Oncology: For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer.Cardiology: For the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging.Neurology: For the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures 1). Oncology: For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer.. Cardiology: For the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging.. Neurology: For the identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures 1). 1.1 Oncology. For assessment of abnormal glucose metabolism to assist in the evaluation of malignancy in patients with known or suspected abnormalities found by other testing modalities, or in patients with an existing diagnosis of cancer. 1.2 Cardiology. For the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function in patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging.. 1.3 Neurology. For the identification of regions of abnormalglucose metabolism associated with foci of epileptic seizures.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 14.1 Oncology. The efficacy of Fludeoxyglucose 18 Injectionin positron emission tomography cancer imaging was demonstrated in16 independent studies. These studies prospectively evaluated the use ofFludeoxyglucose 18 in patients with suspected or known malignancies,including non-small cell lung cancer, colo-rectal, pancreatic, breast, thyroid,melanoma, Hodgkins and non-Hodgkins lymphoma, and various types of metastaticcancers to lung, liver, bone, and axillary nodes. All these studies had at least 50 patients andused pathology as standard of truth. The Fludeoxyglucose 18 Injection dosesin the studies ranged from 200 MBq to 740 MBq with median and mean dose of370 MBq. In the studies, the diagnostic performance ofFludeoxyglucose 18 Injection varied with the type of cancer, size of cancer,and other clinical conditions. Falsenegative and false positive scans were observed. Negative Fludeoxyglucose 18Injection PET scans do not exclude the diagnosis of cancer. Positive Fludeoxyglucose 18 Injection PETscans can not replace pathology to establish diagnosis of cancer. Non-malignant conditions such as fungalinfections, inflammatory processes and benign tumors have patterns of increasedglucose metabolism that may give rise to false-positive scans. The efficacy of Fludeoxyglucose 18Injection PET imaging in cancer screening was not studied. 14.2 Cardiology. The efficacy of Fludeoxyglucose 18 Injectionfor cardiac use was demonstrated in ten independent, prospective studies ofpatients with coronary artery disease and chronic left ventricular systolicdysfunction who were scheduled to undergo coronary revascularization. Before revascularization, patients underwentPET imaging with Fludeoxyglucose 18 Injection (74 370 MBq, - 10 mCi) and perfusionimaging with other diagnostic radiopharmaceuticals. Doses of Fludeoxyglucose F18 Injection ranged from 74-370 MBq (2-10 mCi). Segmental, left ventricular, wall-motion assessments of asynergic areasmade before revascularization were compared in blinded manner to assessmentsmade after successful revascularization to identify myocardial segments withfunctional recovery. Left ventricular myocardial segments werepredicted to have reversible loss of systolic function if they showedFludeoxyglucose 18 accumulation and reduced perfusion (i.e., flow-metabolismmismatch). Conversely, myocardial segments were predicted to have irreversibleloss of systolic function if they showed reductions in both Fludeoxyglucose F18 accumulation and perfusion (i.e., matched defects). Findings of flow-metabolism mismatch in amyocardial segment may suggest that successful revascularization will restoremyocardial function in that segment. However, false-positive tests occur regularly, and the decision to havea patient undergo revascularization should not be based on PET findingsalone. Similarly, findings of matcheddefect in myocardial segment may suggest that myocardial function will notrecover in that segment, even if it is successfully revascularized. However, false-negative tests occur regularly,and the decision to recommend against coronary revascularization, or torecommend cardiac transplant, should not be based on PET findings alone. The reversibility of segmental dysfunction aspredicted with Fludeoxyglucose 18 PET imaging depends on successful coronaryrevascularization. Therefore, in patients with low likelihood of successfulrevascularization, the diagnostic usefulness of PET imaging withFludeoxyglucose 18 Injection is more limited.. 14.3 Neurology. In prospective, open label trial,Fludeoxyglucose 18 Injection was evaluated in 86 patients with epilepsy. Each patient received dose ofFludeoxyglucose 18 Injection in the range of 185-370 MBq (5-10 mCi). The mean age was 16.4 years (range: months- 58 years; of these, 42 patients were less than 12 years and 16 patients wereless than years old). Patients had known diagnosis of complex partialepilepsy and were under evaluation for surgical treatment of their seizuredisorder. Seizure foci had beenpreviously identified on ictal EEGs and sphenoidal EEGs. Fludeoxyglucose 18 Injection PET imagingconfirmed previous diagnostic findings in 16% (14/87) of the patients; in 34%(30/87) of the patients, Fludeoxyglucose 18 Injection PET images provided newfindings. In 32% (27/87), imaging withFludeoxyglucose 18 Injection was inconclusive. The impact of these imagingfindings on clinical outcomes is not known.Several other studies comparing imaging withFludeoxyglucose 18 Injection results to subsphenoidal EEG, MRI and/orsurgical findings supported the concept that the degree of hypometabolismcorresponds to areas of confirmed epileptogenic foci. The safety and effectiveness ofFludeoxyglucose 18 Injection to distinguish idiopathic epileptogenic focifrom tumors or other brain lesions that may cause seizures have not beenestablished.

DESCRIPTION SECTION.

11 DESCRIPTION. 11.1 Chemical Characteristics. Fludeoxyglucose 18 Injection is positron emitting radiopharmaceutical that is used for diagnostic purposes in conjunction with positron emission tomography (PET) imaging. The active ingredient 2-deoxy-2-[ 18F]fluoro-D-glucose has the molecular formula of 6H 11 18FO with molecular weight of 181.26, and has the following chemical structure: Fludeoxyglucose 18 Injection is provided as ready to use sterile, pyrogen free, clear, colorless citrate buffered solution. Each mL contains between 0.740 to 18.5 GBq (20.0-500 mCi) of 2-deoxy-2-[ 18F]fluoro-D-glucose at the EOS, 4.5 mg of sodium chloride in citrate buffer. The pH of the solution is between 4.5 and 7.5. The solution is packaged in multiple-dose glass vial and does not contain any preservative.. Chemical Structure. 11.2 Physical Characteristics. Fluorine 18 has physical half-life of 109.7 minutes and decays to Oxygen 18 (stable) by positron decay. The principal photons useful for imaging are the dual 511 keV annihilation gamma photons that are produced and emitted simultaneously in opposite directions when the positron interacts with an electron (Table 2). Table 2. Principal Radiation Emission Data for Fluorine 18Radiation/Emission%Per DisintegrationMeanEnergyPositron(+)96.73249.8 keVGamma(+-)193.46511.0 keVProduced by positron annihilation From: Kocher, D.C. Radioactive Decay TablesDOE/TIC-I 1026, 89 (1981)The specific gamma ray constant (point sourceair kerma coefficient) for fluorine 18 is 5.7 R/hr/mCi (1.35 10 -6Gy/hr/kBq) at cm. The half-value layer (HVL) for the 511 keV photons is mmlead (Pb). The range of attenuation coefficients for this radionuclide as afunction of lead shield thickness is shown in Table 3. For example, the interpositionof an mm thickness of Pb, with coefficient of attenuation of 0.25, willdecrease the external radiation by 75%. Table 3. Radiation Attenuation of 511 keV Photons by lead (Pb) shieldingShieldthickness (Pb) mmCoefficientof attenuation0 0.00 0.50 0.25 13 0.10 26 0.01 39 0.001 52 0.0001For use in correcting for physical decay of thisradionuclide, the fractions remaining at selected intervals after calibrationare shown in Table 4.Table 4. Physical Decay Chart for Fluorine 18MinutesFraction Remaining0 1.000 15 0.909 30 0.826 60 0.683 110 0.500 220 0.250calibration time.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Fludeoxyglucose F18 Injection emitsradiation. Use procedures to minimizeradiation exposure. Calculate the finaldose from the end of synthesis (EOS) time using proper radioactive decayfactors. Assay the final dose in aproperly calibrated dose calibrator before administration to the patient see Description (11.2)]. Fludeoxyglucose F18 Injection emits radiation. Use procedures to minimize radiationexposure. Screenfor blood glucose abnormalities. Inthe oncology and neurology settings, instruct patients to fast for - hoursprior to the drugs injection. Consider medical therapy and laboratorytesting to assure at least two days of normoglycemia prior to the drugsadministration 5.2). Inthe cardiology setting, administration of glucose-containing food or liquids(e.g., 50 75 grams) prior to thedrugs injection facilitates localization of cardiac ischemia 2.3). Aseptically withdraw Fludeoxyglucose F18 Injectionfrom its container and administer by intravenous injection 2). The recommended dose: for adults is - 10 mCi (185 370 MBq), in allindicated clinical settings 2.1). for pediatric patients is 2.6 mCi in the neurologysetting 2.2). Initiateimaging within 40 minutes following drug injection; acquire static emissionimages 30 100 minutes from time of injection 2). Inthe oncology and neurology settings, instruct patients to fast for - hoursprior to the drugs injection. Consider medical therapy and laboratorytesting to assure at least two days of normoglycemia prior to the drugsadministration 5.2). Inthe cardiology setting, administration of glucose-containing food or liquids(e.g., 50 75 grams) prior to thedrugs injection facilitates localization of cardiac ischemia 2.3). for adults is - 10 mCi (185 370 MBq), in allindicated clinical settings 2.1). for pediatric patients is 2.6 mCi in the neurologysetting 2.2). 2.1 Recommended Dose for Adults. Withinthe oncology, cardiology and neurology settings, the recommended dose foradults is - 10 mCi (185 370 MBq) as an intravenous injection.. 2.2 Recommended Dose for Pediatric Patients. Withinthe neurology setting, the recommended dose for pediatric patients is 2.6 mCi,as an intravenous injection. The optimaldose adjustment on the basis of body size or weight has not been determined see Use in Special Populations (8.4)]. 2.3 Patient Preparation. Tominimize the radiation absorbed dose to the bladder, encourage adequatehydration.Encourage the patient to drink water or other fluids (as tolerated) in the 4hours before their PET study. Encourage the patient to void as soon as theimaging study is completed and as often as possible thereafter for at least onehour.Screenpatients for clinically significant blood glucose abnormalities by obtaining ahistory and/or laboratory tests see Warnings and Precautions (5.2)]. Prior to Fludeoxyglucose 18 PET imaging in the oncology and neurologysettings, instruct patient to fast for - hours prior to the drugsinjection. Inthe cardiology setting, administration of glucose-containing food or liquids(e.g., 50 75 grams) prior to Fludeoxyglucose 18 Injection facilitateslocalization of cardiac ischemia.. Tominimize the radiation absorbed dose to the bladder, encourage adequatehydration.Encourage the patient to drink water or other fluids (as tolerated) in the 4hours before their PET study. Encourage the patient to void as soon as theimaging study is completed and as often as possible thereafter for at least onehour.. Screenpatients for clinically significant blood glucose abnormalities by obtaining ahistory and/or laboratory tests see Warnings and Precautions (5.2)]. Prior to Fludeoxyglucose 18 PET imaging in the oncology and neurologysettings, instruct patient to fast for - hours prior to the drugsinjection. Inthe cardiology setting, administration of glucose-containing food or liquids(e.g., 50 75 grams) prior to Fludeoxyglucose 18 Injection facilitateslocalization of cardiac ischemia.. 2.4 Radiation Dosimetry. The estimated human absorbed radiation doses (rem/mCi) to newborn (3.4 kg), 1-year old (9.8 kg), 5-year old (19 kg), 10-year old (32 kg), 15-year old (57 kg), and adult (70 kg) from intravenous administration of Fludeoxyglucose 18 Injection are shown in Table 1. These estimates were calculated based on human data and using the data published by the International Commission on Radiological Protection for Fludeoxyglucose 18F. The dosimetry data show that there are slight variations in absorbed radiation dose for various organs in each of the age groups. These dissimilarities in absorbed radiation dose are due to developmental age variations (e.g., organ size, location, and overall metabolic rate for each age group). The identified critical organs (in descending order) across all age groups evaluated are the urinary bladder, heart, pancreas, spleen, and lungs. Table 1. Estimated Absorbed Radiation Doses (rem/mCi) After Intravenous Administration of Fludeoxyglucose 18 Injection OrganNewborn (3.4kg) 1-year old (9.8kg) 5-year old (19kg) 10-year old (32kg) 15-year old (57kg) Adult (70kg) Bladder wall 4.31.70.930.600.400.32Heart wall2.41.20.700.440.290.22Pancreas2.20.680.330.250.130.096Spleen2.20.840.460.290.190.14Lungs0.960.380.200.130.0920.064Kidneys0.810.340.190.130.0890.074Ovaries0.800.80.190.110.0580.053Uterus0.790.350.190.120.0760.062LLI wall0.690.280.150.0970.0600.051Liver0.690.310.170.110.0760.058Gallbladder wall0.690.260.140.0930.0590.049Small intestine0.680.290.150.0960.0600.047ULI wall0.670.270.150.0900.0570.046Stomach wall0.650.270.140.0890.0570.047Adrenals0.650.280.150.0950.0610.048Testes0.640.270.140.0850.0520.041Red marrow0.620.260.140.0890.0570.047Thymus0.610.260.140.0860.0560.044Thyroid0.610.260.130.0800.0490.039Muscle0.0580.250.130.0780.0490.039Bone surface0.570.240.120.0790.0520.041Breast0.540.220.110.0680.0430.034Skin0.490.200.100.0600.0370.030Brain0.290.130.090.0780.0720.070Other tissues0.590.250.130.0830.0520.042aMIRDOSE software was used to calculate the radiation absorbed dose. Assumptions on the biodistribution based on data from Gallagher et al. and Jones et al. bThe dynamic bladder model with uniform voiding frequency of 1.5 hours was used. LLI lower large intestine; ULI upper large intestine 2.5 Radiation Safety Drug Handling. Use waterproof gloves, effective radiationshielding, and appropriate safety measures when handling Fludeoxyglucose F18Injection to avoid unnecessary radiation exposure to the patient, occupationalworkers, clinical personnel and other persons.Radiopharmaceuticals should be used by or underthe control of physicians who are qualified by specific training and experiencein the safe use and handling of radionuclides, and whose experience andtraining have been approved by the appropriate governmental agency authorizedto license the use of radionuclides.Calculatethe final dose from the end of synthesis (EOS) time using proper radioactivedecay factors. Assay the final dose in aproperly calibrated dose calibrator before administration to the patient see Description (11.2)]. The dose of Fludeoxyglucose F18 used in givenpatient should be minimized consistent with the objectives of the procedure,and the nature of the radiation detection devices employed.. Use waterproof gloves, effective radiationshielding, and appropriate safety measures when handling Fludeoxyglucose F18Injection to avoid unnecessary radiation exposure to the patient, occupationalworkers, clinical personnel and other persons.. Radiopharmaceuticals should be used by or underthe control of physicians who are qualified by specific training and experiencein the safe use and handling of radionuclides, and whose experience andtraining have been approved by the appropriate governmental agency authorizedto license the use of radionuclides.. Calculatethe final dose from the end of synthesis (EOS) time using proper radioactivedecay factors. Assay the final dose in aproperly calibrated dose calibrator before administration to the patient see Description (11.2)]. The dose of Fludeoxyglucose F18 used in givenpatient should be minimized consistent with the objectives of the procedure,and the nature of the radiation detection devices employed.. 2.6 Drug Preparation and Administration. Calculate the necessary volume to administerbased on calibration time and dose.Aseptically withdraw Fludeoxyglucose F18Injection from its container.Inspect Fludeoxyglucose F18 Injection visuallyfor particulate matter and discoloration before administration, wheneversolution and container permit.Do not administer the drug if it containsparticulate matter or discoloration; dispose of these unacceptable or unusedpreparations in safe manner, in compliance with applicable regulations.Use Fludeoxyglucose 18 Injection within 12hours from the EOS.. Calculate the necessary volume to administerbased on calibration time and dose.. Aseptically withdraw Fludeoxyglucose F18Injection from its container.. Inspect Fludeoxyglucose F18 Injection visuallyfor particulate matter and discoloration before administration, wheneversolution and container permit.. Do not administer the drug if it containsparticulate matter or discoloration; dispose of these unacceptable or unusedpreparations in safe manner, in compliance with applicable regulations.. Use Fludeoxyglucose 18 Injection within 12hours from the EOS.. 2.7 Imaging Guidelines. Initiateimaging within 40 minutes following Fludeoxyglucose 18 Injectionadministration.Acquirestatic emission images 30 100 minutes from the time of injection.. Initiateimaging within 40 minutes following Fludeoxyglucose 18 Injectionadministration.. Acquirestatic emission images 30 100 minutes from the time of injection.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIAL POPULATIONS. Pregnancy Category C: Nohuman or animal data. Consider alternative diagnostics; use only if clearlyneeded 8.1). Nursing mothers: Use alternatives to breast feeding (e.g., storedbreast milk or infant formula) for at least 10 half-lives of radioactive decay,if Fludeoxyglucose 18 Injection is administered to woman who isbreast-feeding 8.3). Pediatric Use: Safety andeffectiveness in pediatric patients have not been established in the oncologyand cardiology settings 8.4). Pregnancy Category C: Nohuman or animal data. Consider alternative diagnostics; use only if clearlyneeded 8.1). Nursing mothers: Use alternatives to breast feeding (e.g., storedbreast milk or infant formula) for at least 10 half-lives of radioactive decay,if Fludeoxyglucose 18 Injection is administered to woman who isbreast-feeding 8.3). Pediatric Use: Safety andeffectiveness in pediatric patients have not been established in the oncologyand cardiology settings 8.4). 8.1 Pregnancy. Pregnancy Category CAnimal reproduction studies have not beenconducted with Fludeoxyglucose 18 Injection. It is also not known whetherFludeoxyglucose 18 Injection can cause fetal harm when administered to apregnant woman or can affect reproduction capacity. Consider alternative diagnostic tests in pregnantwoman; administer Fludeoxyglucose 18 Injection only if clearly needed.. 8.3 Nursing Mothers. It is not known whether Fludeoxyglucose 18Injection is excreted in human milk. Consider alternative diagnostic tests inwomen who are breast-feeding. Usealternatives to breast feeding (e.g., stored breast milk or infant formula) forat least 10 half-lives of radioactive decay, if Fludeoxyglucose 18 Injectionis administered to woman who is breast-feeding.. 8.4 Pediatric Use. The safety and effectiveness of FludeoxyglucoseF 18 Injection in pediatric patients with epilepsy is established on the basisof studies in adult and pediatric patients. In pediatric patients withepilepsy, the recommended dose is 2.6 mCi. The optimal dose adjustment on the basisof body size or weight has not been determined. In the oncology or cardiology settings, thesafety and effectiveness of Fludeoxyglucose 18 Injection have not beenestablished in pediatric patients.