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Long-Term Precision of ¹⁸F-Fluoride PET Skeletal Kinetic Studies in the Assessment of Bone Metabolism

¹ King's College London, Osteoporosis Screening and Research Unit, Guy's Hospital, London, United Kingdom; ² Molecular Medicine Section, National Heart and Lung Institute, Imperial College, London, United Kingdom; ³ Department of Nuclear Medicine, Royal Marsden Hospital, London, United Kingdom; ⁴ School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland; and ⁵ King's College London, PET Imaging Centre, St. Thomas' Hospital, London, United Kingdom

Correspondence: For correspondence or reprints contact: Michelle Frost, Osteoporosis Screening and Research Unit, King's College London, Guy's Hospital Campus, St. Thomas St., London, SE1 9RT, U.K. E-mail: michelle.frost{at}kcl.ac.uk

¹⁸F-Fluoride PET allows noninvasive evaluation of regional bone metabolism and has the potential to become a useful tool for assessing patients with metabolic bone disease and evaluating novel drugs being developed for these diseases. The main PET parameter of interest, termed K_i, reflects regional bone metabolism. The aim of this study was to compare the long-term precision of ¹⁸F-fluoride PET with that of biochemical markers of bone turnover assessed over 6 mo. Methods: Sixteen postmenopausal women with osteoporosis or significant osteopenia and a mean age of 64 y underwent ¹⁸F-fluoride PET of the lumbar spine and measurements of biochemical markers of bone formation (bone-specific alkaline phosphatase and osteocalcin) and bone resorption (urinary deoxypyridinoline) at baseline and 6 mo later. Four different methods for analyzing the ¹⁸F-fluoride PET data were compared: a 4k 3-compartmental model using nonlinear regression analysis (K_i-4k), a 3k 3-compartmental model using nonlinear regression analysis (K_i-3k), Patlak analysis (K_i-PAT), and standardized uptake values. Results: With the exception of a small but significant decrease in K_i-3k at 6 mo, there were no significant differences between the baseline and 6-mo values for the PET parameters or biochemical markers. The long-term precision, expressed as the coefficient of variation (with 95% confidence interval in parentheses), was 12.2% (9%–19%), 13.8% (10%–22%), 14.4% (11%–22%), and 26.6% (19%–40%) for K_i-3k, K_i-PAT, mean standardized uptake value, and K_i-4k, respectively. For comparison, the precision of the biochemical markers was 10% (7%–15%), 18% (13%–27%), and 14% (10%–21%) for bone-specific alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline, respectively. Intraclass correlation between the baseline and 6-mo values ranged from 0.44 for K_i-4k to 0.85 for K_i-3k. No significant correlation was found between the repeated mean standardized uptake value measurements. Conclusion: The precision and intraclass correlation observed for K_i-3k and K_i-PAT was equivalent to that observed for biochemical markers. This study provided initial data on the long-term precision of ¹⁸F-fluoride PET measured at the lumbar spine, which will aid in the accurate interpretation of changes in regional bone metabolism in response to treatment.

Key Words: ¹⁸F-fluoride PET • precision • bone metabolism • osteoporosis

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