Abstract
90
Objectives: Fibrous dysplasia (FD) is a benign skeletal disorder characterized by the replacement of normal bone and normal bone marrow with abnormal fibro-osseous tissue leading to bone deformity, fractures, disability and pain. 18F-NaF is a bone seeking PET-radiopharmaceutical with favorable pharmacokinetics, which is taken up by bone through (18F-) ions exchange with hydroxyl ions (OH-) on the surface of hydroxyapatite. Bone areas of abnormally increased 18F-NaF activity reflect underlying processes characterized by increased bone surface exposed to blood flow, like the processes encountered in FD. Aim of the current study was to explore potential associations between the activity of 18F-NaF positive FD lesions in the entire skeleton with the serum levels of established markers of bone activity, such as alkaline phosphatase (Alk Phos) and osteocalcin (OC), and urine levels of N-terminal telopeptide (NTX).
Methods: Fifteen FD patients underwent whole-body 18F-NaF PET/CT studies at the NIH Clinical Center (Fig. 1A). PET scans from the vertex of the skull to the plantar surface of the feet were obtained on dedicated PET/CT scanners, 62.36 ± 6.11 (mean ± SD) minutes (range: 58 - 76) after intravenous administration of an average ± standard deviation (SD) of 2.81 ± 0.83 mCi of 18F-NaF (range: 0.92 - 4.98). Low dose, non-contrast, non-diagnostic CT scans were acquired for localization and attenuation correction purposes. FD-related 18F-NaF activity was assessed by using MIM vista (version 6.5.9). Firstly, a VOI (volume of interest) encompassing the entire skeleton was drawn, and afterwards a SUVmax threshold-based approach -customized per patient- was employed in order to include all FD-related bone uptake. Automatic lesion demarcation generated by the software was compared with the lesions’ anatomic cross-sectional images, to achieve maximal overlap between functional and anatomic images. Separate VOIs encircling all areas above the SUVmax threshold set by the user, were automatically generated and areas with physiologic or non-FD related 18F-NaF activity (e.g. activity in the urinary tract) were manually removed by an experienced nuclear medicine physician. Subsequently, FD-related 18F-NaF activity in the entire skeleton determined as the product of SUVmean multiplied by the total volume (TV) of all skeletal 18F-NaF positive FD lesions (TA = SUVmean × TV) was obtained automatically.
Results: Pearson’s correlation test revealed that FD-related 18F-NaF activity in the entire skeleton was positively associated with serum levels of alkaline phosphatase (r = 0.758, P < 0.01) (Fig. 1B), osteocalcin (r = 0.707, P = 0.01) (Fig. 1C), and urine levels of NTX (r = 0.739, P = 0.02) (Fig. 1D). (P-values adjusted for false discovery rate)
Conclusions: Skeletal FD-related 18F-NaF activity strongly correlates with bone turnover markers, indicating that 18F-NaF PET/CT imaging precisely reflects underlying bone metabolic processes encountered in FD. This data strongly implies the application of this imaging modality in the in vivo assessment of FD activity, holding promise to serve as a surrogate endpoint for accurate determination of disease activity.