4.2. Posology and method of administration Posology

The radioactivity usually recommended for adults is 2-5 MBq/kg of body mass depending on the PET(/CT) machine in use and acquisition mode, administered by direct intravenous injection. Paediatric population Only few clinical data are available for patients aged under 18 years concerning the safety and diagnostic effi cacy of this product. The use in paediatric children and adolescents has to be considered carefully, based upon clinical needs and assessing the risk/benefi t ratio in this patient group. The activities to be administered to children and adolescents may be calculated according to the recommendations of the EANM paediatric task group :

• Three dimension acquisition mode is recommended Administred activity [MBq] = 14 x multiple (in table below), minimal activity = 14MBq
• in case only 2 dimension acquisition mode is only available, the formula will be :

Administred activity [MBq] = 25.9 x multiple (in table below), minimal activity = 26MBq
3 kg = 1.00 12 kg = 3.14 22 kg = 5.29 32 kg = 7.29 42 kg = 9.14 52-54 kg = 11.29
4 kg = 1.14 14 kg = 3.57 24 kg = 5.71 34 kg = 7.72 44 kg = 9.57 56-58 kg = 12.00
6 kg = 1.71 16 kg = 4.00 26 kg = 6.14 36 kg = 8.00 46 kg = 10.00 60-62 kg = 12.71
8 kg = 2.14 18 kg = 4.43 28 kg = 6.43 38 kg = 8.43 48 kg = 10.29 64-66 kg = 13.43
10 kg = 2.71 20 kg = 4.86 30 kg = 6.86 40 kg = 8.86 50 kg = 10.71 68 kg = 14.00

Patients with renal impairement Extensive dose-range and adjustment studies with this product in normal and special populations have not been performed. The pharmacokinetics of sodium fl uoride-(18F) in renally-impaired patients has not been characterised. Method of administration For patient preparation, see section 4.4. The activity of sodium fl uoride-(18F) has to be measured with an activimeter immediately prior to injection. The injection must be intravenous in order to avoid irradiation as a result of local extravasation, as well as imaging artefacts. Image acquisition The emission scans are usually started 60 minutes after the injection of sodium fl uoride-(18F). Provided a suffi cient activity remains for adequate counting statistics, sodium fl uoride-(18F) PET can also be performed up to two or three hours after administration, thus reducing background activity. Voiding immediately prior to imaging is recommended in order to reduce the activity in the pelvis. If required, sodium fl uoride-(18F) PET examinations can be repeated within a short period of time.

4.3. Contraindications

• Hypersensitivity to the active substance, to any of the excipients or to any of the components of the labelled radiopharmaceutical.
• Pregnancy

4.4. Special warnings and precautions for use

Pregnancy, see section

4.6 Individual benefi t/risk justifi cation

For each patient, the radiation exposure must be justifi able by the likely benefi t. The activity administered should in every case be as low as reasonably achievable to obtain the required diagnostic information. In patients with reduced kidney function, careful consideration of the indication is required since an increased radiation exposure is possible in these patients. Paediatric population Paediatric population, see section 4.2. Careful consideration of the indication is required since the effective dose per MBq is higher in children than in adults (see section 11. Dosimetry)

Patient preparation

The patient should be well hydrated before the start of the examination and urged to void as often as possible during the fi rst hours after the study in order to reduce radiation. Interpretation of sodium fl uoride (18F)-PET images Sodium fl uoride (18F) has a higher sensitivity for the detection of bone lesions than other ìbone-seekingî tracers (99mTc-labeled phosphate and phosphonic acid derivatives). Since sodium fl uoride (18F) does not show secondary cancerous processes directly, but notifi es cancer effects (osteogenic activity following osseous lesions), sodium fl uoride (18F) is less effective for the detection of early stages of bone metastases, like bone marrow metastases without substantial bone damage. Hardware fusion of the functional sodium fl uoride (18F) PET images with morphologic images e.g. PET-CT can lead to an increased sensitivity and specifi city in bone diagnostics. As there is no signifi cant difference in uptake by malignant or benign lesions, the differentiation between bone metastases and non-malignant bone lesions benefi ts from the analysis of PET and CT image fusion, better obtained from hybrid PET/CT imaging, or if not available from supplemental diagnostic procedures (MRI, CT).

General warnings

It is recommended to avoid any close contact between the patient and young children during the initial 12 hours following the injection. Radiopharmaceuticals should be received, used and administered only by authorised persons in designated clinical settings. Their receipt, storage, use, transfer and disposal are subject to the regulations and/or appropriate licences of the competent offi cial organisation. Radiopharmaceuticals should be prepared by the user in a manner which satisfi es both radiation safety and pharmaceutical quality requirements. Appropriate aseptic precautions should be taken. Sodium fl uoride (18F) should be stored and handled in adequate shielding, so as to protect patients and hospital staff as much as possible. In particular, it is recommended to protect oneself from the effects of beta+ radiation and annihilation photons by using an appropriate shielding when performing withdrawals from the vial and injections.

Specific warnings

According to the time of conditioning injection for the patient, the content of sodium may in some cases be greater than 1 mmol (23mg). This should be taken into account in patient on low sodium diet. 4.5. Interaction with other medicinal products and other forms of interaction. No interaction studies have been performed.

4.6. Fertility, pregnancy and lactation

Women of childbearing potential When an administration of radiopharmaceuticals to a woman of childbearing potential is intended, it is important to determine whether or not she is pregnant. Any woman who has missed a period should be assumed to be pregnant until proven otherwise. If in doubt about her potential pregnancy (if the woman has missed a period, if the period is very irregular, etc.), alternative techniques not using ionising radiation (if there are any) should be offered to the patient. Breastfeeding Before administering radiopharmaceuticals to a mother who is breastfeeding consideration should be given to the possibility of delaying the administration of radionuclide until the mother has ceased breastfeeding, and to what is the most appropriate choice of radiopharmaceuticals, bearing in mind the secretion of activity in breast milk. If the administration is considered necessary, breastfeeding should be interrupted for 12 hours and the expressed feeds discarded. Close contact with infants should be restricted during this period.

4.7. Effects on ability to drive and use machines

Not relevant.

4.8. Undesirable effects

No serious undesirable effects have been observed after the administration of sodium fl uoride (18F) to date. Since the administered substance quantity is very low, the major risk is caused by the radiation exposure. Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. As the effective dose is approx. 8,9 mSv when the maximal recommended activity of 370 MBq is administered, these adverse events are expected to occur with a low probability.

4.9. Overdose

In the event of administration of a radiation overdose with sodium fl uoride-(18F) the absorbed dose to the patient should be reduced where possible by increasing the elimination of the radionuclide from the body by forced diuresis and frequent bladder voiding. It might be helpful to estimate the effective dose that was applied.