SODIUM FLUORIDE F18

11.1 Chemical Characteristics Sodium Fluoride F-18 Injection, USP, is a positron emitting radiopharmaceutical, containing no-carrier-added, radioactive fluoride F-18 that is used for diagnostic purposes in conjunction with PET imaging. It is administered by intravenous injection. The active ingredient, sodium fluoride F-18, has the molecular formula Na[ 18 F] with a molecular weight of 40.99, and has the following chemical structure: Na +18 F – Sodium Fluoride F-18 Injection, USP, is provided as a ready-to-use, isotonic, sterile, pyrogen-free, preservative-free, clear and colorless solution. Each mL of the solution contains between 370 MBq to 7,400 MBq (10 mCi to 200 mCi) sodium fluoride F-18, at the EOS reference time, in 0.9% aqueous sodium chloride. The pH of the solution is between 4.5 and 8. The solution is presented in 30 mL multiple-dose glass vials with variable total volume and total radioactivity in each vial. 11.2 Physical Characteristics Fluoride F-18 decays by positron (β+) emission and has a half-life of 109.7 minutes. Ninety-seven percent of the decay results in emission of a positron with a maximum energy of 633 keV and 3% of the decay results in electron capture with subsequent emission of characteristic X-rays of oxygen. 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 2 ). Fluorine F-18 atom decays to stable 18 O-oxygen. Table 2. Principal Emission Data for Fluoride F-18 Radiation/Emission % Per Disintegration Mean Energy Positron(β+) 96.73 249.8 keV Gamma(±) Produced by positron annihilation From: Kocher, D.C. Radioactive Decay Data Tables DOE/TIC-11026, 69, 1981 193.46 511.0 keV The specific gamma ray constant for fluoride 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 4.1 mm lead (Pb) or 2.9 mm tungsten (W) alloy. A range of values for the attenuation of radiation results from the interposition of various thickness of Pb or Tungsten alloy. The range of attenuation coefficients for this radionuclide is shown in Table 3 . For example, the interposition of an 8.3 mm thickness of Pb or 5.8 mm thickness of W alloy 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) and Tungsten (W) alloy shielding Shield Thickness (Pb) mm Shield Thickness (W) Alloy mm Coefficient of Attenuation 0 0 0.00 4 3 0.50 8 6 0.25 13 9 0.10 26 19 0.01 39 28 0.001 53 37 0.0001 Table 4 lists the fraction of radioactivity remaining at selected time intervals from the calibration time. This information may be used to correct for physical decay of the radionuclide. Table 4. Physical Decay Chart for Fluoride F-18 Time Since Calibration Fraction Remaining 0 calibration time 1.00 15 minutes 0.909 30 minutes 0.826 60 minutes 0.683 110 minutes 0.500 220 minutes 0.250 440 minutes 0.060 12 hours 0.011 24 hours 0.0001

Sodium Fluoride F-18 Injection, USP, is indicated for diagnostic positron emission tomography (PET) imaging of bone to define areas of altered osteogenic activity. Sodium Fluoride F-18 Injection, USP, is a radioactive diagnostic agent for positron emission tomography (PET) indicated for imaging of bone to define areas of altered osteogenic activity ( 1 ).

• Sodium Fluoride F-18 Injection, USP, emits radiation and must be handled with appropriate safety measures ( 2.1 ). • Administer 300-450 MBq (8–12 mCi) as an intravenous injection in adults ( 2.4 ). • Administer approximately 2.1 MBq/kg in children with a minimum of 19 MBq (0.5 mCi) and a maximum of 148 MBq (4 mCi) as an intravenous injection ( 2.5 ). • Imaging can begin 1–2 hours after administration; optimally at one hour post administration ( 2.7 ). • Encourage patients to void immediately prior to imaging the lumbar spine and bony pelvis ( 2.7 ). 2.1 Radiation Safety - Drug Handling • Wear waterproof gloves and effective shielding when handling Sodium Fluoride F-18 Injection, USP. Use appropriate safety measures, including shielding, consistent with proper patient management 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. • Use aseptic technique to maintain sterility during all operations involved in the manipulation and administration of Sodium Fluoride F-18 Injection, USP. • The dose of Sodium Fluoride F-18 Injection, USP, should be minimized consistent with the objectives of the procedure, and the nature of the radiation detection devices employed. • The final dose for the patient should be calculated using proper decay factors from the time of End of Synthesis (EOS), and measured by a suitable radioactivity calibration system before administration [ see Description ( 11.2 ) ]. 2.2 Radiation Safety - Patient Preparation • To minimize the radiation-absorbed dose to the bladder, encourage adequate hydration. Encourage the patient to ingest at least 500 mL of fluid immediately prior and subsequent to the administration of Sodium Fluoride F-18 Injection, USP. • Encourage the patient to void one-half hour after administration of Sodium Fluoride F-18 Injection, USP, and as frequently thereafter as possible for the next 12 hours. 2.3 Drug Preparation and Administration • Calculate the necessary volume to administer based on calibration time and dose. • Inspect Sodium Fluoride F-18 Injection, USP, visually for particulate matter and discoloration before administration, whenever solution and container permit. • Do not administer Sodium Fluoride F-18 Injection, USP, containing particulate matter or discoloration; dispose of these unacceptable or unused preparations in a safe manner, in compliance with applicable regulations. • Aseptically withdraw Sodium Fluoride F-18 Injection, USP, from its container. 2.4 Recommended Dose for Adults Administer 300–450 MBq (8–12 mCi) as an intravenous injection. 2.5 Recommended Dose for Pediatric Patients In reported clinical experience in approximately 100 children, weight based doses (2.1 MBq/kg) ranging from 19 MBq–148 MBq (0.5 mCi–4 mCi) were used. 2.6 Radiation Dosimetry The age/weight- based estimated absorbed radiation doses (mGy/MBq) from intravenous injection of Sodium Fluoride F-18 Injection, USP, are shown in Table 1 . These estimates were calculated based on human data and using the data published by the Nuclear Regulatory Commission [ 1 ] and the International Commission on Radiological Protection for Sodium Fluoride Injection [ 2 ]. The bone, bone marrow and urinary bladder are considered target and critical organs. Table 1. Estimated Absorbed Radiation Doses after Intravenous Administration of Sodium Fluoride F-18 Injection, USP Organ Estimated Radiation Dose mGy/MBq Adult 70 kg Data from Nuclear Regulatory Commission Report, Radiation Dose Estimates for Radiopharmaceuticals , NUREG/CR-6345, page 10, 1996. 15 year 56.8 kg Data from ICRP publication 53, Radiation Dose to Patients from Radiopharmaceuticals , Ann ICRP, Volume 18, pages 15 and 74, 1987. 10 year 33.2 kg 5 year 19.8 kg 1 year 9.7 kg Adrenals 0.0062 0.012 0.018 0.028 0.052 Brain 0.0056 N/A N/A N/A N/A Bone surfaces 0.060 0.050 0.079 0.13 0.30 Breasts 0.0028 0.0061 0.0097 0.015 0.030 GI Gallbladder wall 0.0044 N/A N/A N/A N/A Stomach wall 0.0038 0.008 0.013 0.019 0.036 Small intestine 0.0066 0.012 0.018 0.028 0.052 Upper large intestine wall 0.0058 0.010 0.016 0.026 0.046 Lower large intestine wall 0.012 0.016 0.025 0.037 0.063 Heart wall 0.0039 N/A N/A N/A N/A Kidneys 0.019 0.025 0.036 0.053 0.097 Liver 0.0040 0.0084 0.013 0.021 0.039 Lungs 0.0041 0.0084 0.013 0.020 0.039 Muscle 0.0060 N/A N/A N/A N/A Ovaries 0.011 0.016 0.023 0.036 0.063 Pancreas 0.0048 0.0096 0.015 0.023 0.044 Red marrow 0.028 0.053 0.088 0.18 0.38 Skin 0.0040 N/A N/A N/A N/A Spleen 0.0042 0.0088 0.014 0.021 0.041 Testes 0.0078 0.013 0.021 0.033 0.062 Thymus 0.0035 N/A N/A N/A N/A Thyroid 0.0044 0.0084 0.013 0.020 0.036 Urinary bladder wall 0.25 0.27 0.4 0.61 1.1 Uterus 0.019 0.023 0.037 0.057 0.099 Other tissue N/A 0.010 0.015 0.024 0.044 Effective Dose Equivalent mSv/MBq 0.027 0.034 0.052 0.086 0.17 2.7 Imaging Guidelines • Imaging of Sodium Fluoride F-18 Injection, USP, can begin 1–2 hours after administration; optimally at 1 hour post administration. • Encourage the patient to void immediately prior to imaging the fluoride F-18 radioactivity in the lumbar spine or bony pelvis.

None None ( 4 ).

No adverse reactions have been reported for Sodium Fluoride F-18 Injection, USP, based on a review of the published literature, publicly available reference sources, and adverse drug reaction reporting systems. However, the completeness of these sources is not known. No adverse reactions have been reported for Sodium Fluoride F-18 Injection, USP, based on a review of the published literature, publicly available reference sources, and adverse drug reaction reporting systems ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Cardinal Health at 1-800-618-2768 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

The possibility of interactions of Sodium Fluoride F-18 Injection, USP, with other drugs taken by patients undergoing PET imaging has not been studied.