(18)F-sodium fluoride (NaF) as an imaging tracer portrays calcium metabolic activity either in the osseous structures or in soft tissue. Currently, clinical use of NaF-PET is confined to detecting metastasis to the bone, but this approach reveals indirect evidence for disease activity and will have limited use in the future in favor of more direct approaches that visualize cancer cells in the read marrow where they reside. This has proven to be the case with FDG-PET imaging in most cancers. However, a variety of studies support the application of NaF-PET to assess benign osseous diseases. In particular, bone turnover can be measured from NaF uptake to diagnose osteoporosis. Several studies have evaluated the efficacy of bisphosphonates and their lasting effects as treatment for osteoporosis using bone turnover measured by NaF-PET. Additionally, NaF uptake in vessels tracks calcification in the plaques at the molecular level, which is relevant to coronary artery disease. Also, NaF-PET imaging of diseased joints is able to project disease progression in osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. Further studies suggest potential use of NaF-PET in domains such as back pain, osteosarcoma, stress-related fracture, and bisphosphonate-induced osteonecrosis of the jaw. The critical role of NaF-PET in disease detection and characterization of many musculoskeletal disorders has been clearly demonstrated in the literature, and these methods will become more widespread in the future. The data from PET imaging are quantitative in nature, and as such, it adds a major dimension to assessing disease activity.
In a healthy body, homeostatic actions of osteoclasts and osteoblasts maintain the integrity of the skeletal system. When cellular activities of osteoclasts and osteoblasts become abnormal, pathological bone conditions, such as osteoporosis, can occur. Traditional imaging modalities, such as radiographs, are insensitive to the early cellular changes that precede gross pathological findings, often leading to delayed disease diagnoses and suboptimal therapeutic strategies. 18F-sodium fluoride (18F-NaF)-positron emission tomography (PET) is an emerging imaging modality with the potential for early diagnosis and monitoring of bone diseases through the detection of subtle metabolic changes. Specifically, the dissociated 18F- is incorporated into hydroxyapatite, and its uptake reflects osteoblastic activity and bone perfusion, allowing for the quantification of bone turnover. While 18F-NaF-PET has traditionally been used to detect metastatic bone disease, recent literature corroborates the use of 18F-NaF-PET in benign osseous conditions as well. In this review, we discuss the cellular mechanisms of 18F-NaF-PET and examine recent findings on its clinical application in diverse metabolic, autoimmune, and osteogenic bone disorders.
We aimed to determine whether NaF-PET/CT or FDG-PET/CT can detect abdominal aortic molecular calcification and inflammation in patients with rheumatoid arthritis (RA). Methods:In this study, 18 RA patients (4 women, 14 men; mean age 56.011.7) and 18 healthy controls (4 women, 14 men; mean age 55.8 11.9) were included. The controls were matched to patients by sex and age (4 years). All subjects of this study underwent NaF-PET/CT scanning 90 minutes following the administration of NaF. FDG-PET/CT imaging was performed 180 minutes following intravenous FDG injection. Using OsiriX software, the global mean standardized uptake value (global SUVmean) in abdominal aorta was calculated for both FDG and NaF. The NaF SUVmean and FDG SUVmean were divided by the blood pool activity providing target-tobackground ratios (TBR) namely, NaF-TBRmean and FDG-TBRmean. The CT calcium volume score was obtained using a growing region algorithm based on Hounsfield units. Results:The average NaF-TBRmean score among RA patients was significantly greater than that of healthy controls (median 1.61; IQR: 1.49-1.88 vs median 1.40; IQR: 1.23-1.52, P= 0.002). The average CT calcium volume score among RA patients was also significantly greater than that of healthy controls (median 1.96 cm 3 ; IQR 0.57-5.48 vs median 0.004 cm 3 ; IQR 0.04-0.05, P< 0.001).There was no significant difference between the average FDG-TBRmean scores in the RA patients when compared to healthy controls (median 1.29; IQR 1.13-1.52 vs median 1.29; IQR 1.13-1.52, P=0.98). Conclusion:Quantitative assessment with NaF-PET/CT identifies increased molecular calcification in the wall of the abdominal aorta among patients with RA as compared with healthy controls, while quantitative assessment with FDG-PET/CT did not identify a difference in aortic vessel wall FDG uptake between the RA and healthy control groups.
The introduction of total body (TB) PET/CT instruments over the past 2 years has initiated a new and exciting era in medical imaging. These instruments have substantially higher sensitivity (up to 68 times) than conventional modalities and therefore allow imaging the entire body over a short period. However, we need to further refine the imaging protocols of this instrument for different indications. Total body PET will allow accurate assessment of the extent of disease, particularly, including the entire axial and appendicular skeleton. Furthermore, delayed imaging with this instrument may enhance the sensitivity of PET for some types of cancer. Also, this modality may improve the detection of venous thrombosis, a common complication of cancer and chemotherapy, in the extremities and help prevent pulmonary embolism. Total body PET allows assessment of atherosclerotic plaques throughout the body as a systematic disease. Similarly, patients with widespread musculoskeletal disorders including both oncologic and nononcologic entities, such as degenerative joint disease, rheumatoid arthritis, and osteoporosis, may benefit from the use of TB-PET. Finally, quantitative global disease assessment provided by this approach will be superior to conventional measurements, which do not reflect overall disease activity. In conclusion, TB-PET imaging may have a revolutionary impact on day-to-day practice of medicine and may become the leading imaging modality in the future.
Aim: 2-deoxy-2-[ 18 F]fluoro-d-glucose positron emission tomography/computed tomography (FDG-PET/CT) can portray increased glycolysis due to inflammation in rheumatoid arthritis (RA). The aim of this study was to evaluate and compare the reliability and construct validity of two methods of quantifying RA disease activity using FDG-PET/CT. Method:Nineteen RA patients and 19 healthy controls matched to sex and age underwent prospective FDG-PET/CT imaging. Metabolic and volumetric metrics were calculated using fixed and adaptive thresholding techniques and partial volume correction. Fixed thresholds segmented regions above average maximum physiological uptake in controls. Differences of means between RA and controls were assessed using t tests, and discrimination was assessed using receiver operating characteristics. Spearman correlation analysis was used to assess associations between FDG- PET/CT measures and clinical assessments of disease activity.Results: All FDG-PET/CT measures were substantially different and nearly non-overlapping between RA and controls (all P < .001). Area under the curve (AUC) for adaptive threshold parameters ranged from 0.986 to 0.997, and AUC for fixed threshold parameters ranged from 0.898 to 0.945. PET parameters were found to correlate positively with various clinical features, namely C-reactive protein, erythrocyte sedimentation rate, interleukin (IL)-6, IL-1, and swollen joint count.
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