*3.6. 18F-Sodium Fluoride (18F-NaF)*

18F-NaF is a highly sensitive biomarker of bone reconstruction, with potential indications in a wide range of bone disease [71–74]. The uptake of the tracer in bone occurs by chemisorption onto hydroxyapatite, followed by exchange with hydroxyl groups in the hydroxyapatite, resulting in formation of fluoroapatite. The tracer accumulates in nearly all sites of increased new bone formation, reflecting regional blood flow, osteoblastic activity and bone turnover [71,75,76].

An increasing interest has been raised in the last years on the potential application of 18F-NaF PET/CT in MM diagnostics and management. This interest was based, however, on a very small number of studied MM patients without comparison with a robust reference imaging method [77–80]. Despite this initial enthusiasm, subsequent publications demonstrated rather discouraging results. In particular, 18F-NaF PET/CT did not confer any superiority or complementarity to 18F-FDG PET/CT in detection of MM lesions, showing both lower sensitivity and specificity [81–83]. Moreover, 18F-NaF PET/CT does not seem to add significantly to 18F-FDG PET/CT in the treatment response evaluation of MM patients, as shown in a study of 34 patients undergoing high-dose chemotherapy and ASCT [84].

The low sensitivity of 18F-NaF PET/CT in detecting myeloma lesions is mainly attributed to the fact that the tracer indicates osteoblastic activity. However, since the hallmark of MM is the osteolytic lesion, the accumulation of 18F-NaF takes place only in the accompanying, sometimes minimal, reactive osteoblastic changes [85]. Further, being a very sensitive radiopharmaceutical for osteoblastic activity, 18F-NaF accumulates in practically in every site of newly mineralizing bone, irrelevant of its aetiology. This means that any cause of bone reconstruction, such as traumatic or degenerative bone lesions, will lead to tracer accumulation, significantly decreasing its specificity as a myeloma tracer [86].
