Fludeoxyglucose F18 by is a Prescription medication manufactured, distributed, or labeled by THE FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH. Drug facts, warnings, and ingredients follow.
Fludeoxyglucose F18 Injection is indicated for positron emission tomography (PET) imaging in the following settings:
Fludeoxyglucose F18 Injection emits radiation. Use procedures to minimize radiation
exposure. Screen
for blood glucose abnormalities.
Aseptically withdraw Fludeoxyglucose F18 Injection from its container and administer by intravenous injection (2). The recommended dose:
Initiate imaging within 40 minutes following drug injection; acquire static emission images 30 – 100 minutes from time of injection (2).
Multiple-dose glass vial containing 0.74 – 11.1 GBq (20 – 300 mCi/mL) of Fludeoxyglucose F18 Injection and 4.5 mg of sodium chloride in citrate buffer (approximately 16 – 17 mL volume), for intravenous administration (3).
None. (4)
Hypersensitivity reactions
have occurred; have emergency resuscitation equipment and personnel immediately
available ( 6).
To report SUSPECTED ADVERSE REACTIONS, contact The Feinstein Institute for Medical Research at 516-562-1042 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 1/2012
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)].
Within the oncology, cardiology and neurology settings, the recommended dose for adults is 5 – 10 mCi (185 – 370 MBq) as an intravenous injection.
Within 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)].
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.
Organ | Newborn (3.4kg) | 1-year old (9.8kg) | 5-year old (19kg) | 10-year old (32kg) | 15-year old (57kg) | Adult (70kg) |
Bladder wallb | 4.3 | 1.7 | 0.93 | 0.60 | 0.40 | 0.32 |
Heart wall | 2.4 | 1.2 | 0.70 | 0.44 | 0.29 | 0.22 |
Pancreas | 2.2 | 0.68 | 0.33 | 0.25 | 0.13 | 0.096 |
Spleen | 2.2 | 0.84 | 0.46 | 0.29 | 0.19 | 0.14 |
Lungs | 0.96 | 0.38 | 0.20 | 0.13 | 0.092 | 0.064 |
Kidneys | 0.81 | 0.34 | 0.19 | 0.13 | 0.089 | 0.074 |
Ovaries | 0.80 | 0.8 | 0.19 | 0.11 | 0.058 | 0.053 |
Uterus | 0.79 | 0.35 | 0.19 | 0.12 | 0.076 | 0.062 |
LLI wall* | 0.69 | 0.28 | 0.15 | 0.097 | 0.060 | 0.051 |
Liver | 0.69 | 0.31 | 0.17 | 0.11 | 0.076 | 0.058 |
Gallbladder wall | 0.69 | 0.26 | 0.14 | 0.093 | 0.059 | 0.049 |
Small intestine | 0.68 | 0.29 | 0.15 | 0.096 | 0.060 | 0.047 |
ULI wall** | 0.67 | 0.27 | 0.15 | 0.090 | 0.057 | 0.046 |
Stomach wall | 0.65 | 0.27 | 0.14 | 0.089 | 0.057 | 0.047 |
Adrenals | 0.65 | 0.28 | 0.15 | 0.095 | 0.061 | 0.048 |
Testes | 0.64 | 0.27 | 0.14 | 0.085 | 0.052 | 0.041 |
Red marrow | 0.62 | 0.26 | 0.14 | 0.089 | 0.057 | 0.047 |
Thymus | 0.61 | 0.26 | 0.14 | 0.086 | 0.056 | 0.044 |
Thyroid | 0.61 | 0.26 | 0.13 | 0.080 | 0.049 | 0.039 |
Muscle | 0.058 | 0.25 | 0.13 | 0.078 | 0.049 | 0.039 |
Bone surface | 0.57 | 0.24 | 0.12 | 0.079 | 0.052 | 0.041 |
Breast | 0.54 | 0.22 | 0.11 | 0.068 | 0.043 | 0.034 |
Skin | 0.49 | 0.20 | 0.10 | 0.060 | 0.037 | 0.030 |
Brain | 0.29 | 0.13 | 0.09 | 0.078 | 0.072 | 0.070 |
Other tissues | 0.59 | 0.25 | 0.13 | 0.083 | 0.052 | 0.042 |
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)].
In 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.
Pregnancy Category C
Animal 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.
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.
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.
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
ingredient 2-deoxy-2-[18F]fluoro-D-glucose
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.
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).
Radiation/Emission | % Per Disintegration | Mean Energy |
Positron(β+) | 96.73 | 249.8 keV |
Gamma(±)* | 193.46 | 511.0 keV |
*Produced by positron annihilation
From: 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%.
Shield thickness (Pb) mm | Coefficient of attenuation |
0 | 0.00 |
4 | 0.50 |
8 | 0.25 |
13 | 0.10 |
26 | 0.01 |
39 | 0.001 |
52 | 0.0001 |
For use in correcting for physical decay of this radionuclide, the fractions remaining at selected intervals after calibration are shown in Table 4.
Minutes | Fraction Remaining |
0* | 1.000 |
15 | 0.909 |
30 | 0.826 |
60 | 0.683 |
110 | 0.500 |
220 | 0.250 |
*calibration time
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 be hypometabolic.
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)].
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 established.
Fludeoxyglucose F 18 Injection is supplied in a multi-dose, capped 20 mL 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 16 - 17 mL. The contents of each vial are sterile, pyrogen-free and preservative-free.
NDC 13267-123 -23
This 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.
FLUDEOXYGLUCOSE F18
fludeoxyglucose f18 injection |
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Labeler - THE FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH (110565913) |