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European Nuclear Medicine Guide
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European Nuclear Medicine Guide
Chapter 4.2

Sodium fluoride ([18F]NaF)

4.2.1 Radiopharmaceutical

  • [18F]NaF also known as,
    • sodium [18F]fluoride
    • [18F]NaF

4.2.2 Uptake mechanism / biology of the tracer

[18F]NaF is a bone-seeking PET radiopharmaceutical that binds to sites of bone formation. 18F-NaF uptake reflects bone blood flow and osteoblastic activity. After i.v. injection, [18F]NaF is rapidly cleared from the plasma and excreted by the kidneys. [18F]NaF bone uptake is related to blood flow and almost all 1[18F]NaF delivered is retained by bone after a single pass of blood, resulting in an almost 100% first-pass extraction. The bone uptake of [18F]NaF is double that of 99mTc-MDP [87]. This is reflected in high target-to-background ratios. Approximately 30% of the injected dose is found in RBCs, which does not interfere with bone uptake, as [18F]NaF freely diffuses across the cell membrane. Approximately 50% of the injected [18F]NaF is taken up in bone, and after chemisorption onto hydroxyapatite, the fluoride ions (18F-) exchange rapidly with hydroxyl ions (OH-) in the surface of the hydroxyapatite matrix and form fluoroapatite.

4.2.3 Indications

  • Overall, indications of [18F]NaF PET/CT are similar to 99mTc-MDP bone scintigraphy. Nonetheless, [18F]NaF plasma clearance is faster and bone uptake is 2-fold higher than [99mTc]Tc-MDP, and PET provides 3-dimensional images with higher resolution resulting in higher diagnostic performance of [18F]NaF PET/CT compared to standard bone scintigraphy. Yet, due to the higher cost of PET/CT and limited availability of PET/CT systems, differences in indications exist between individual countries depending on their healthcare systems.
  • [18F]NaF may be used for the detection of malignant bony lesions and the determination of the extent of the disease. Data are available on the use of 18F-NaF PET/CT in benign bone diseases and indications have been suggested in certain individuals with metabolic or inflammatory bone diseases or orthopaedic disorders.
  • [18F]NaF PET/CT may be of particular value in special patient populations where imaging with radiolabelled bisphosphonates is hampered, for example in end-stage renal disease or morbidly obese patients [88].

4.2.4 Contra-indications

  • Examinations involving ionizing radiation should be avoided in pregnant women, unless the potential benefits outweigh the radiation risk to the mother and foetus.

4.2.5 Clinical performances

Overall, diagnostic performance of [18F]NaFPET/CT is superior to conventional bone scintigraphy. In malignant diseases, [18F]NaFPET/CT has been more extensively studied in prostate cancer that is usually a non-FDG-avid tumour with highly prevalent osteoblastic bone metastases.

Osteomedullary malignant lesions can be missed if neither bone formation is seen with [18F]NaF PET nor sufficient bone destruction (osteolysis) to be observed on CT images.

4.2.6 Activities to administer

The suggested activities to administer are:

  • [18F]NaF in adults: 1.5-3.7 MBq/kg; 185-370 MBq

In paediatric nuclear medicine, the activities should be modified according to the EANM paediatric dosage card (https://www.eanm.org/publications/dosage-calculator/). The minimum recommended activity to administer is 14 MBq and the maximum level should not exceed 185 MBq.

4.2.7 Dosimetry

The effective dose for [18F]NaF in adults is 17 µSv/MBq [3]. The organ with the highest absorbed dose is the urinary bladder wall: 150 µGy/MBq. In children (1 year old) the ED is: 110 µSv/MBq, with the largest absorbed doses in urinary bladder (540 µGy/MBq) and bone surfaces (480 µGy/MBq).

The range in effective dose in adults for [18F]NaF is: 3.1-6.3 mSv per procedure.

The radiation exposure related to a CT scan carried out as part of a [18F]NaF PET/CT study depends on the intended use of the CT study and may differ from patient to patient. Radiation exposure associated with the CT component used for attenuation correction and localization is variable and depends on the length of the scan and x-ray tube parameters commonly adapted to patient’s body mass index.

Caveat:
“Effective Dose” is a protection quantity that provides a dose value related to the probability of health detriment to an adult reference person due to stochastic effects from exposure to low doses of ionizing radiation. It should not be used to quantify the radiation risk for a single individual associated with a particular nuclear medicine examination. It is used to characterize a certain examination in comparison to alternatives, but  it should be emphasized that if the actual risk to a certain patient population is to be assessed, it is mandatory to apply risk factors (per mSv) that are appropriate for the gender, the age distribution and the disease state of that population."

4.2.8 Interpretation criteria/major pitfalls

Similar to bone scintigraphy, [18F]NaF PET has low specificity, and any cause of bone formation and/or increased regional blood flow induces [18F]NaF uptake, e.g. trauma, post-surgical changes, degenerative disease, and infection. Nevertheless, the CT component of PET/CT allows morphologic characterization of lesions and improves diagnostic confidence to differentiate malignant from benign bone lesions.

The “flare phenomenon” can also be observed after treatment initiation. It normally starts soon (7-10 days) after therapy commencement and could last for up to 6 months.

SUV measurement is not routinely used in interpretation of studies.

Quantitative assessment of bone metabolism using [18F]NaFPET is under clinical investigation.

4.2.9 Patient preparation

Patient preparation is the same as for bone scintigraphy. Patients do not need to fast, may take all their usual medications, and should be well hydrated (2 or more glasses of water within 1h before the examination and another 2 or more glasses after injection) to promote rapid excretion of the radiopharmaceutical.

4.2.10 Methods

Imaging parameters are similar to [18F]FDG PET/CT. Acquisition can start 30-45 min after radiopharmaceutical injection for the axial skeleton, however, it is recommended to start later, after 90-120 min, for imaging of extremities. Acquisition time per bed position will vary depending on the amount of injected radioactivity, uptake time, body mass index, body habitus of the patient, and camera factors. To obtain high - quality skeletal images on current devices, emission scans with acquisition times of 1-2 min per bed position in 3D mode are performed depending on the above-mentioned parameters. The detailed recommendations are available in the (18)F-NaF PET/CT: EANM Procedure Guidelines for Bone Imaging [89]  and SNM Practice Guideline for Sodium [18F]FDG PET/CT Bone Scans 1.0  [90].