The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.
1 Indications And Usage
Fludeoxyglucose F18 Injection is indicated for positron
emission tomography (PET) imaging in the following settings:
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.
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.
For the identification of regions of abnormal
glucose metabolism associated with foci of epileptic seizures.
2 Dosage And Administration
Fludeoxyglucose F18 Injection emits
radiation. Use procedures to minimize
radiation exposure. Calculate the final
dose from the end of synthesis (EOS) time using proper radioactive decay
factors. Assay the final dose in a
properly calibrated dose calibrator before administration to the patient [ see Description (11.2)].
2.1 Recommended Dose For Adults
the oncology, cardiology and neurology settings, the recommended dose for
adults is 5 – 10 mCi (185 – 370 MBq) as an intravenous injection.
2.2 Recommended Dose For Pediatric Patients
the neurology setting, the recommended dose for pediatric patients is 2.6 mCi,
as an intravenous injection. The optimal
dose adjustment on the basis of body size or weight has not been determined [ see Use in Special Populations (8.4)].
2.3 Patient Preparation
- Minimize the radiation absorbed dose to the bladder, encourage adequate
- Hydration.Encourage the patient to drink water or other fluids (as tolerated) in the 4
- Hours before their PET study.Encourage the patient to void as soon as the
- Imaging study is completed and as often as possible thereafter for at least one
- Patients for clinically significant blood glucose abnormalities by obtaining a
- History and/or laboratory tests [ see Warnings and Precautions (5.2)]. Prior to Fludeoxyglucose F 18 PET imaging in the oncology and neurology
- Settings, instruct patient to fast for 4 – 6 hours prior to the drug’s
- The cardiology setting, administration of glucose-containing food or liquids
- (e.g., 50 – 75 grams) prior to Fludeoxyglucose F 18 Injection facilitates
- Localization of cardiac ischemia.
2.4 Radiation Dosimetry
The estimated human absorbed radiation doses
(rem/mCi) to a 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 F 18 Injection are shown in Table 1. These
estimates were calculated based on human2
data and using the data published by the International Commission on
Radiological Protection4 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 F 18 InjectionaOrganNewborn(3.4kg)1-year old(9.8kg)5-year old
(57kg)Adult(70kg)Bladder wallb126.96.36.1990.600.400.32Heart wall188.8.131.520.440.290.22Pancreas2.20.680.330.250.130.096Spleen2.20.840.460.290.190.14Lungs0.960.380.200.130.0920.064Kidneys0.810.340.190.130.0890.074Ovaries0.800.80.190.110.0580.053Uterus0.790.350.190.120.0760.062LLI wall*0.690.280.150.0970.0600.051Liver0.690.310.170.110.0760.058Gallbladder wall0.690.260.140.0930.0590.049Small intestine0.680.290.150.0960.0600.047ULI wall**0.670.270.150.0900.0570.046Stomach 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 2 software was used to calculate the radiation
absorbed dose. Assumptions on the biodistribution based on data from Gallagher
et al.1 and Jones et al.2bThe dynamic bladder model with a uniform voiding
frequency of 1.5 hours was used.*LLI = lower large intestine; **ULI = upper large
2.5 Radiation Safety – Drug Handling
- Use waterproof gloves, effective radiation
- Shielding, and appropriate safety measures when handling Fludeoxyglucose F18
- Injection to avoid unnecessary radiation exposure to the patient, occupational
- Workers, clinical personnel and other persons.Radiopharmaceuticals should be used by or under
- The control of physicians who are qualified by specific training and experience
- In the safe use and handling of radionuclides, and whose experience and
- Training have been approved by the appropriate governmental agency authorized
- To license the use of radionuclides.Calculate
- The final dose from the end of synthesis (EOS) time using proper radioactive
- Decay factors. Assay the final dose in a
- Properly calibrated dose calibrator before administration to the patient [ see Description (11.2)].The dose of Fludeoxyglucose F18 used in a given
- Patient 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 administer
- Based on calibration time and dose.Aseptically withdraw Fludeoxyglucose F18
- Injection from its container.Inspect Fludeoxyglucose F18 Injection visually
- For particulate matter and discoloration before administration, whenever
- Solution and container permit.Do not administer the drug if it contains
- Particulate matter or discoloration; dispose of these unacceptable or unused
- Preparations in a safe manner, in compliance with applicable regulations.Use Fludeoxyglucose F 18 Injection within 12
- Hours from the EOS.
2.7 Imaging Guidelines
- Imaging within 40 minutes following Fludeoxyglucose F 18 Injection
- Static emission images 30 – 100 minutes from the time of injection.
3 Dosage Forms And Strengths
Multiple-dose glass vial containing 0.74 - 11.1GBq (20 - 300 mCi/mL) of Fludeoxyglucose F 18 Injection and 4.5 mg of sodium chloride in citrate buffer (approximately 29 mL volume) for intravenous administration.
5.1 Radiation Risks
Radiation-emitting products, including Fludeoxyglucose
F 18 Injection, may increase the risk for cancer, especially in pediatric
patients. Use the smallest dose
necessary for imaging and ensure safe handling to protect the patient and
health care worker [ see Dosage and Administration (2.5)].
5.2 Blood Glucose Abnormalities
the oncology and neurology setting, suboptimal imaging may occur in patients
with inadequately regulated blood glucose levels. In these patients, consider medical therapy
and laboratory testing to assure at least two days of normoglycemia prior to Fludeoxyglucose
F 18 Injection administration.
6 Adverse Reactions
Hypersensitivity reactions with pruritus, edema
and rash have been reported in the post-marketing setting. Have emergency resuscitation equipment and
personnel immediately available.
7 Drug Interactions
possibility of interactions of Fludeoxyglucose F 18 Injection with other drugs
taken by patients undergoing PET imaging has not been studied.
Pregnancy Category CAnimal reproduction studies have not been
conducted with Fludeoxyglucose F 18 Injection. It is also not known whether
Fludeoxyglucose F 18 Injection can cause fetal harm when administered to a
pregnant woman or can affect reproduction capacity. Consider alternative diagnostic tests in a pregnant
woman; administer Fludeoxyglucose F 18 Injection only if clearly needed.
8.3 Nursing Mothers
It is not known whether Fludeoxyglucose F 18
Injection is excreted in human milk. Consider alternative diagnostic tests in
women who are breast-feeding. Use
alternatives to breast feeding (e.g., stored breast milk or infant formula) for
at least 10 half-lives of radioactive decay, if Fludeoxyglucose F 18 Injection
is administered to a woman who is breast-feeding.
8.4 Pediatric Use
The safety and effectiveness of Fludeoxyglucose
F 18 Injection in pediatric patients with epilepsy is established on the basis
of studies in adult and pediatric patients. In pediatric patients with
epilepsy, the recommended dose is 2.6 mCi. The optimal dose adjustment on the basis
of body size or weight has not been determined.In the oncology or cardiology settings, the
safety and effectiveness of Fludeoxyglucose F 18 Injection have not been
established in pediatric patients.
11.1 Chemical Characteristics
Fludeoxyglucose F 18 Injection is a positron
emitting radiopharmaceutical that is used for diagnostic purposes in
conjunction with positron emission tomography (PET) imaging. The active
has the molecular formula of C6H1118FO5 with a molecular weight of 181.26, and has the
following chemical structure:Fludeoxyglucose F 18 Injection is provided as a
ready to use sterile, pyrogen free, clear, colorless citrate buffered solution.
Each mL contains between 0.740 to 11.1GBq (20.0-300 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 a multiple-dose glass vial and
does not contain any preservative.
11.2 Physical Characteristics
Fluorine F 18 has a physical half-life of 109.7 minutes and decays to Oxygen O 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 F 18Radiation/Emission%
EnergyPositron(β+)96.73249.8 keVGamma(±)*193.46511.0 keV*Produced by positron annihilationFrom: Kocher, D.C. Radioactive Decay Tables
DOE/TIC-I 1026, 89 (1981)The specific gamma ray constant (point source
air kerma coefficient) for fluorine F 18 is 5.7 R/hr/mCi (1.35 x 10 -6
Gy/hr/kBq) at 1 cm. The half-value layer (HVL) for the 511 keV photons is 4 mm
lead (Pb). The range of attenuation coefficients for this radionuclide as a
function of lead shield thickness is shown in Table 3. For example, the interposition
of an 8 mm thickness of Pb, with a coefficient of attenuation of 0.25, will
decrease the external radiation by 75%.Table 3. Radiation Attenuation of 511 keV Photons by lead (Pb) shieldingShield
thickness (Pb) mmCoefficient
of attenuation00.0040.5080.25130.10260.01390.001520.0001For use in correcting for physical decay of this
radionuclide, the fractions remaining at selected intervals after calibration
are shown in Table 4.Table 4. Physical Decay Chart for Fluorine F 18MinutesFraction Remaining0*1.000150.909300.826600.6831100.5002200.250*calibration time
12.1 Mechanism Of Action
Fludeoxyglucose F 18 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 F 18 is transported through the cell membrane by facilitative
glucose transporter proteins and is phosphorylated within the cell to [18F] 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 F 18 reflect a balance
involving glucose transporter, hexokinase and glucose-6-phosphatase activities.
When allowance is made for the kinetic differences between glucose and
Fludeoxyglucose F 18 transport and phosphorylation (expressed as the ''lumped
constant'' ratio), Fludeoxyglucose F 18 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 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.
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 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 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 F 18 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
Distribution: In four healthy male volunteers, receiving an
intravenous administration of 30 seconds in duration, the arterial blood level
profile for Fludeoxyglucose F 18 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 11.6 (±) 1.1 min, and 80-95 minutes with a
mean and STD of 88 (±) 4 min.Plasma protein binding of Fludeoxyglucose F 18
has not been studied.Metabolism: Fludeoxyglucose
F 18 is transported into cells and phosphorylated to [18F]-FDG-6-
phosphate at a rate proportional to the rate of glucose utilization within that
tissue. [F 18]-FDG-6-phosphate presumably is metabolized to 2-deoxy-2-[F
18]fluoro-6-phospho-D-mannose([F 18]FDM-6-phosphate).Fludeoxyglucose F 18 Injection 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 F 18 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 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.Elimination: 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.Special Populations: The pharmacokinetics of Fludeoxyglucose F 18
Injection have not been studied in renally-impaired, hepatically impaired or
pediatric patients. Fludeoxyglucose F 18 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 F 18 distribution in humans have not been ascertained [ see Warnings and Precautions (5.2)].
13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility
Animal studies have not been performed to
evaluate the Fludeoxyglucose F 18 Injection carcinogenic potential, mutagenic
potential or effects on fertility.
The efficacy of Fludeoxyglucose F 18 Injection
in positron emission tomography cancer imaging was demonstrated in
16 independent studies. These studies prospectively evaluated the use of
Fludeoxyglucose F 18 in patients with suspected or known malignancies,
including 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. All these studies had at least 50 patients and
used pathology as a standard of truth. The Fludeoxyglucose F 18 Injection doses
in the studies ranged from 200 MBq to 740 MBq with a median and mean dose of
370 MBq.In the studies, the diagnostic performance of
Fludeoxyglucose F 18 Injection varied with the type of cancer, size of cancer,
and other clinical conditions. False
negative and false positive scans were observed. Negative Fludeoxyglucose F 18
Injection PET scans do not exclude the diagnosis of cancer. Positive Fludeoxyglucose F 18 Injection PET
scans can not replace pathology to establish a diagnosis of cancer. Non-malignant conditions such as fungal
infections, inflammatory processes and benign tumors have patterns of increased
glucose metabolism that may give rise to false-positive scans. The efficacy of Fludeoxyglucose F 18
Injection PET imaging in cancer screening was not studied.
The efficacy of Fludeoxyglucose F 18 Injection
for cardiac use was demonstrated in ten independent, prospective studies of
patients with coronary artery disease and chronic left ventricular systolic
dysfunction who were scheduled to undergo coronary revascularization. Before revascularization, patients underwent
PET imaging with Fludeoxyglucose F 18 Injection (74 – 370 MBq, 2 – 10 mCi) 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 in a blinded manner to assessments
made after successful revascularization to identify myocardial segments with
functional recovery.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 reductions in both Fludeoxyglucose F
18 accumulation and perfusion (i.e., matched defects).Findings of flow-metabolism mismatch in a
myocardial segment may 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 may 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 more limited.
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). The mean age was 16.4 years (range: 4 months
- 58 years; of these, 42 patients were less than 12 years and 16 patients were
less than 2 years old). Patients had a known diagnosis of complex partial
epilepsy and were under evaluation for surgical treatment of their seizure
disorder. Seizure foci had been
previously identified on ictal EEGs and sphenoidal EEGs. Fludeoxyglucose F 18 Injection PET imaging
confirmed previous diagnostic findings in 16% (14/87) of the patients; in 34%
(30/87) of the patients, Fludeoxyglucose F 18 Injection PET images provided new
findings. In 32% (27/87), imaging with
Fludeoxyglucose F 18 Injection was inconclusive. The impact of these imaging
findings on clinical outcomes 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
- Gallagher B.M., Ansari A., Atkins H., Casella V., Christman D.R., Fowler
- J.S., Ido T., MacGregor R.R., Som P., Wan C.N., Wolf A.P., Kuhl D.E., and Reivich
- M. “Radiopharmaceuticals XXVII.
- 18F-labeled 2-deoxy-2-fluoro-d-glucose as a radiopharmaceutical for measuring
- Regional myocardial glucose metabolism in vivo: tissue distribution and imaging
- Studies in animals,” J Nucl Med,
- 1977; 18, 990-6.Jones S.C.,
- Alavi, A., Christman D., Montanez, I., Wolf, A.P., and Reivich M. “The radiation dosimetry of 2 [F-18]
- Fluoro-2-deoxy-D-glucose in man,” J
- Nucl Med, 1982; 23, 613-617.Kocher, D.C.
- “Radioactive Decay Tables: A handbook of
- Decay data for application to radiation dosimetry and radiological
- Assessments,” 1981, DOE/TIC-I 1026, 89.ICRP Publication 53, Volume 18, No. l-4,1987,
- Pages 75-76.
16 How Supplied/Storage And Handling
Fludeoxyglucose F 18 Injection is supplied in a multi-dose, capped glass vial containing between 0.740 – 11.1GBq/mL (20 - 300 mCi/mL), of no carrier added 2-deoxy-2-[F 18] fluoro-D-glucose, at end of synthesis, in approximately 29 mL. The contents of each vial are sterile, pyrogen-free and preservative-free.NDC 69815-754-50This radiopharmaceutical is licensed by the State of New York, Department Of Health, Bureau of Environmental Radiation Protection, for distribution to persons licensed pursuant to New York's Regulatory Code for Radioactive material specified in Chapter 1-Part 16 of the State Sanitary Code, as appropriate, or under equivalent licenses of an Agreement State or Licensing State.Store the Fludeoxyglucose F 18 Injection vial upright in a lead shielded container at 25°C (77°F); excursions permitted to 15-30°C (59-86°F).Store and dispose of Fludeoxyglucose F 18 Injection in accordance with the regulations and a general license, or its equivalent, of an Agreement State or a Licensing State.The expiration date and time are provided on the container label. Use Fludeoxyglucose F 18 Injection within 12 hours from the EOS time.
17 Patient Counseling Information
- Instruct patients in procedures that increase
- Renal clearance of radioactivity. Encourage patients todrink water or other fluids (as tolerated) in
- The 4 hours before their PET study.void as soon as the imaging study is completed
- And as often as possible thereafter for at least one hour.
Manufactured & Distributed by: Memorial Sloan Kettering Cancer CenterRadiochemistry & Molecular Imaging Probes Core FacilityNew York, NY 10065
* Please review the disclaimer below.