Bridging bones: unraveling spondyloarthritis through visualization of new bone formation with fluoride PET/CT

Chapter 2 presents the evaluation of the feasibility of utilizing whole-body [18F]Fluoride PET/CT for visualizing molecular new bone formation in clinically active PsA patients. This tracer effectively captures areas of molecular new bone formation associated with osteoblastic activity, encompassing all domains where PsA disease activity can manifest (peripheral joints, entheses and axial skeleton). A noteworthy finding is that a considerable proportion of the PET-positive joints and entheses sites was not associated with clinical symptoms. These results illustrate the potential of [18F]Fluoride PET/CT to be a novel tool to detect (subclinical) whole-body disease activity in the bone in all disease domains of PsA, depicted in one scan. In chapter 3, the ability of whole-body [18F]Fluoride PET/CT to detect a change in lesional [18F]Fluoride uptake, following 12 weeks of anti-TNF therapy in clinically active PsA patients is described. This study provides confirmation that [18F]Fluoride PET effectively identifies change of molecular new bone formation in PsA patients with active disease. Additionally, it demonstrated the potential of [18F]Fluoride PET to monitor short-term changes in molecular new bone formation, reflecting osteoblastic activity, throughout the entire skeleton of PsA patients. Chapter 4 focusses on validating simplified measures for quantifying [18F]Fluoride in SpA patients in the currently applied dynamic imaging protocol, to reduce patient burden and increase the accessibility of this imaging technique for clinical practice. The preferred outcome measures for quantifying [18F]Fluoride uptake are SUVmean and SUVpeak. Future analysis have yet to show whether similar simplification is also possible in longitudinal studies. In chapter 5 a cross-sectional comparative analysis is performed between the three imaging techniques [18F]Fluoride PET, MRI and CR in patients with clinically active AS. Ten patients underwent a [18F]Fluoride PET/CT scan, MRI scan and CR of the spine and SI-joints. The results highlight that [18F]Fluoride PET captures AS activity that is partly distinct from the findings observed on MRI and CR. Importantly, it also visualizes lesions beyond the scope of MRI and CR. The concurrence between PET positivity and BME on MRI, as well as ankylosis on CR, suggests a link between bone formation and both acute inflammation and more chronic, structural damage. In chapter 6, the assessment and classification of [18F]Fluoride uptake in AS lesions versus degenerative lesions, that may also show local tracer uptake, was investigated in a longitudinal dataset (before and during treatment with biologicals). The longitudinal observations show that the applied visual classification methodology with concordant scoring by two reviewers performed rather well, assuming that the likelihood of decrease of [18F]Fluoride uptake during biological treatment is indeed higher in AS related lesions than in degenerative lesions. Chapter 7 addresses our response to previous reported findings regarding the use of [18F]Fluoride PET/MRI for monitoring therapeutic effects on anti-TNF therapy in AS patients. By highlighting our considerations and suggesting further sub-analysis, we aim to contribute to optimized and ideally standardized [18F]Fluoride scan protocols in SpA patients as well as to comprehensive evaluation and interpretation of therapeutic effects observed using [18F]Fluoride PET/MRI in SpA patients undergoing anti-TNF therapy. In conclusion, this thesis has successfully demonstrated the value of [18F]Fluoride PET imaging in the spectrum of SpA. The findings underscore the potential of [18F]Fluoride PET as an effective modality for visualizing and assessing osteoblastic activity and associated molecular new bone formation in patients with SpA, both in the axial skeleton and at peripheral skeletal sites. The data underline the promising value of [18F]Fluoride PET for future implementation into clinical practice, after further future validation.