The value of ¹⁸F-fluoride PET in bone metastases: an overview

Bone metastases are a major cause of morbidity in patients with advanced cancer, making accurate detection essential for staging, treatment planning, and response assessment. Among molecular imaging techniques, ¹⁸F-sodium fluoride (¹⁸F-NaF) PET/CT is one of the most sensitive modalities for evaluating osteoblastic skeletal metastases because of its rapid blood clearance and high bone uptake identifying areas of increased bone remodeling associated with metastatic disease. Despite its excellent diagnostic performance, the clinical role of ¹⁸F-NaF PET/CT has evolved with the emergence of disease-specific PET radiotracers and advances in hybrid imaging. This review provides a comprehensive overview of the biological basis and imaging principles of ¹⁸F-NaF PET/CT, followed by comparison with other imaging modalities, including conventional bone scintigraphy, SPECT/CT, CT, whole-body MRI and other PET/CT tracers, highlighting the advantages and limitations of each modality. Clinical applications of ¹⁸F-NaF PET/CT in bone metastatic disease is discussed across malignancies. Limitations and pitfalls relevant to interpretation and clinical use of ¹⁸F-NaF PET/CT are reviewed, including false-positive and false-negative findings, artifacts, the flare phenomenon, cost and limited availability, and radiation dose considerations. Finally, advances in quantitative PET imaging, artificial intelligence, and hybrid imaging are discussed as promising tools to improve the diagnostic performance and clinical utility of ¹⁸F-NaF PET/CT. This review highlights the current evidence supporting the use of ¹⁸F-NaF PET/CT and discusses its evolving role in the imaging evaluation of bone metastases.