Label: FLUDEOXYGLUCOSE F-18- fludeoxyglucose f-18 injection injection

Fludeoxyglucose F18 Injection, USP is a positron emitting radiopharmaceutical containing no-carrier added radioactive 2-deoxy-2-[ 18F]fluoro-D-glucose that is used for diagnostic purposes in conjunction with Positron Emission Tomography (PET). It is administered by intravenous injection.

The active ingredient 2-deoxy-2-[ 18F]fluoro-D-glucose, abbreviated [ 18F]FDG, has a molecular formula of C 8H 1118F0 8 with a molecular weight of 181.26 daltons, and has the following chemical structure:

Fludeoxyglucose F18 Injection, USP is provided as a ready to use sterile, pyrogen free, clear, colorless solution. Each milliliter contain between 150 to 1850 MBq (4 — 500 mCi) of 2-deoxy-2-[ 18F]fluoro-D-glucose at the end of synthesis (EOS), and 9 mg of sodium chloride in citrate buffer. The pH of the solution is between 4.5 to 7.5. The solution is packaged in a multiple-dose glass vial and does not contain any preservative.

Fluorine F 18 decays by positron ( +) emission and has a half life of 110 minutes. The principal photons useful for diagnostic imaging are the 511 keV gamma photons, resulting from the interaction of the emitted positron with an electron (Table 1)

*Produced by positron annihilation

From: Kocher, D.C. "Radioactive Decay Tables" DOE/TIC-11026, 89 (1981).

The specific gamma ray constant for Fluorine F 18 is 6.0 R/hr/mCi (0.3 Gy/hr/kBq) at 1cm. The half-value layer (HVL) for the 511 keV photons is 4.1 mm lead (Pb). A range of values for the attenuation of radiation results from the interposition of various thicknesses of Pb.

The range of attenuation coefficients for this radionuclide is shown in Table 2. For example the interposition of an 8.3 mm thickness of Pb, with a coefficient of attenuation of 0.25, will decrease the external radiation by 75%.

For use in correcting for physical decay of this radionuclide, the fractions remaining at selected intervals after calibration are shown in Table 3.

In a prospective, open label trial, [ 18F]FDG was evaluated in 86 patients with epilepsy. Each patient received a dose of [ 18F]FDG 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-[ 18F]FDG findings were confirmed by [ 18F]FDG; 34% (30/87) of patients, [ 18F]FDG scans provided new findings. In 32% (27/87), [ 18F]FDG scans were not definitive. The influence of these findings on surgical outcome; medical management or behavior is not known.

In several other studies comparing [ 18F]FDG scan results to subsphenoidal EEG, MRI and/or surgical findings, the degree of hypometabolism corresponded to areas of confirmed epileptogenic foci.

Fludeoxyglucose F 18 Injection,USP is indicated in PET (positron emission tomography) for:

1. Identification of regions of abnormal glucose metabolism associated with foci of epileptic seizures.

2. 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.

3. Assessment of patients with coronary artery disease and left ventricular dysfunction, when used together with myocardial perfusion imaging, for the identification of left ventricular myocardium with residual glucose metabolism and reversible loss of systolic function.

Fludeoxyglucose F 18 Injection, USP is not indicated for distinguishing epileptogenic foci from brain tumors or other brain lesions which may cause seizures.

None known

None known

The [ 18F]FDG safety data base was evaluated for 374 patients. Of these, 245 were male and 105 were female. For 24 patients, gender was not specified. The mean age was 47.8 years (range under 2 to over 65 years). Eighteen patients were between the age of 0 and 2 years; 42 patients were between the ages of 2 and 21 years old; 213 patients were between 21 and 65 years old and 98 patients were older than 65 years and the ages of 3 male patients were not specified. A racial distribution is not available. In this database, adverse drug reactions that required medical intervention were not reported.

In a small, 42 patient subset of the 374 patients studied, 4 patients had transient hypotension, 6 had hypo- or hyperglycemia and 3 had transient increases in alkaline phosphatase.

[ 18F]FDG uptake may be changed by fasting or by blood sugar changes associated with diabetic mellitus. Blood glucose levels should be stabilized in non-diabetic patients by fasting before [ 18F]FDG injection. Diabetic patients may need stabilization of blood glucose on the day preceding and on the day of the [ 18F]FDG scan.

The recommended dose of [ 18F]FDG for an adult (70 kg) is within the range 185-370 MBq (5-10 mCi), intravenous injection. In children doses as low as 2.6 mCi have been given. Optimal dose reductions for children have not been confirmed.

The optimum rate of administration and upper safe dose for [ 18F]FDG have not been established. The time interval between doses of [ 18F]FDG should be long enough to allow substantial decay (physical and biological) of previous administrations.

It is recommended that PET imaging be initiated within 40 minutes of [ 18F]FDG injection.

The final dose for the patient should be calculated using proper decay factors from the time of the EOS, and measured by a suitable radioactivity calibration system before administration. See decay factors in Table 3.

[ 18F]FDG, like other parenteral drug products, should be inspected visually for particulate matter and discoloration before administration, whenever solution and container permit. Preparations containing particulate matter or discoloration should not be administered. They should be disposed of in a safe manner, in compliance with applicable regulations.

[ 18F]FDG should be stored upright in a lead shielded environment at controlled room temperature.

Aseptic techniques and effective shielding should be employed in withdrawing doses for administration to patients. Waterproof gloves and effective shielding should be worn when handling the product.

Overdoses of [ 18F]FDG have not been-reported. See Radiation Dosimetry Section for related information.

The estimated absorbed radiation doses to an average human adult (70 kg) from intravenous injection of 185 MBq (5 mCi) and 370 MBq (10 mCi) of [ 18F]FDG are shown in Table 4. These estimates were calculated based on human 1 data and using the data published by the International Commission on Radiological Protection 2 for [ 18F]FDG.

*With void 1 hour after administration **With void 2 hours after administration.

The [18F]FDG Effective dose equivalent (Adult)2 is 0.027 mSv/MBq.

1Jones, S.C. , Alavi, A., Christman, D., Montanez, I., Wolf, A.P., and Reivich, M. (1982). The Radiation Dosimetry of 2-F-18 fluoro-2-deoxy-D-glucose in man. J. Nucl. Med. 23, 613-617.

2ICRP Publication 53, Volume 18, No. 1-4, 1987, page 76.

NDC 24468-001-10

Fludeoxyglucose F18 Injection, USP is supplied in a multi-dose, septum capped 10 mL glass vial containing between 148 - 1480 MBq/mL (4 — 500 mCi/mL) of no carrier added 2-deoxy-2-[ 18F]fluoro-D-glucose at end of synthesis, in approximately 6 mL.

This radiopharmaceutical is licensed by the North Dakota Department of Health for distribution to persons authorized to receive the licensed material pursuant to the terms and conditions of a specific license issued by the U.S. Nuclear Regulatory Commission or an Agreement State.