Role of ¹⁸F-NaF PET/CT

Musculoskeletal · 3 min read

¹⁸F-NaF is the oldest bone tracer in nuclear medicine and, in PET form, the sharpest. It answers exactly the question a ^99mTc diphosphonate scan answers — is there tumour anywhere in the skeleton — faster and with markedly better sensitivity. What it does not do is change the question.

Mechanism of action

• Fluoride is chemisorbed onto newly mineralising bone, exchanging with a hydroxyl group of hydroxyapatite to form fluoroapatite.
• The same mechanism as a ^99mTc diphosphonate, one step further — fluoride exchanges into the crystal lattice itself.
• First-pass extraction approaches 100%; protein binding is negligible.
• Skeletal uptake is roughly twice that of a diphosphonate; plasma clearance is rapid.
• Uptake depends on blood flow and exposed mineralising surface — nothing else.

Indications

SNMMI practice guideline for sodium ¹⁸F-fluoride PET/CT bone scans:

• Osteoblastic skeletal metastases — staging, restaging, and an equivocal bone scan.
• Back pain in children and adolescents, particularly suspected spondylolysis.
• Occult or stress fracture, and unexplained bone pain.
• Osteomyelitis, osteonecrosis and bone-graft viability.
• The painful joint prosthesis.
• Benign bone disease — Paget’s, fibrous dysplasia — and abnormal radiographs needing a functional answer.

Protocol and performance

• 185–370 MBq; uptake 45–60 minutes; vertex to mid-thigh or whole body with low-dose CT.
• Hydrate and void — renal excretion, as with a diphosphonate.
• About 4–6 mSv, plus 1–4 mSv for the CT.

More lesions is not the same as more disease

• NaF finds more lesions than bone scintigraphy, and a higher proportion of them are benign — fluoride is at least as avid for degenerative change, and PET resolution finds more of it.
• Without the CT that extra sensitivity becomes false positives, and specificity falls well below the figures above.
• It images the osteoblastic reaction, not the tumour: myeloma is not staged with it, and aggressive renal and thyroid metastases can be photopenic.
• Flare — for two to three months after effective therapy, repair looks like progression.

NaF, or a tumour-seeking tracer?

• NaF images the skeleton’s reaction to tumour; FDG and PSMA image the tumour itself, so they find the marrow and lytic disease NaF cannot.
• In high-risk prostate cancer, PSMA PET/CT reached 92% accuracy against 65% for bone scan plus CT (proPSMA). Where PSMA is available, NaF is not the staging test.
• So NaF’s place is narrow: where you would have done a bone scan, need its sensitivity, and a tumour-seeking tracer is unavailable or unsuitable for that tumour.

Fuller version, with the bone scan it replaces: Metastatic bone survey.