[18F]Fluoride PET-CT imaging for detection and monitoring of bone fomration in spondyloarthritis

One of the hallmarks of disease activity in spondyloarthritis (SpA), a spectrum of rheumatological diseases including ankylosing spondylitis (AS) and psoriatic arthritis (PsA), is new bone formation. Enthesitis and bone formation are related to functional disability on the long term. SpA is a complex disease, as evidenced by the involvement of axial and peripheral articular structures, extra-articular manifestations, presence of co-morbidities such as osteoporosis and vascular inflammation and the histopathological combination of inflammation, tissue destruction, and new tissue formation. Mechanistic understanding of which ‘targetable’ pathways steer these different disease manifestations is required to optimize and tailor treatment to all these different facets of the disease.
Both TNFα and IL-17 are pivotal pathogenic cytokines in SpA. Therapeutic inhibition of each of these cytokines leads to both significant improvement of clinical symptoms and suppression of inflammation in SpA. Studies show that anti-TNF decreases inflammatory activity, and may inhibit progression of bone formation after longer use. Anti-IL-17 treatment, such as Secukinumab, has a very promising profile to inhibit not only inflammatory activity, but potentially also bone formation.
In order to investigate therapeutic effects of Secukinumab on enthesitis and related bone formation, sensitive imaging techniques are required for monitoring early in the course of treatment. Conventional X-rays and CT-scans still play an important role for determination and monitoring of structural damage, but these techniques have limitations. CT-scans do not allow assessment of the whole skeleton in one imaging session, and X-rays are more suited to provide information on long-term changes in bone formation. Both MRI and ultrasound (US) can be applied for evaluation of inflammatory activity, however US is limited to more superficial, peripheral sites that are accessible by this technique, and MRI is less sensitive for bone formation imaging in SpA.
Positron emission tomography (PET) is a promising alternative for bone formation imaging. The technique allows sensitive and quantitative imaging of functional tissue changes in the whole body by targeting specific binding sites. The visualisation of pathophysiology using specific tracers makes PET potentially suitable for early detection of disease activity, even before anatomic changes appear. In addition, it allows quantification of disease activity in order to accurately monitor therapeutic effects. Recently, our group found that disease activity of AS on PET-CT was clearly depicted with the tracer [18F]Fluoride with obvious superior targeting as compared to the reference tracers. [18F]Fluoride uptake in bone reflects local blood flow and regional osteoblastic activity because uptake takes place in the form of hydroxyapatite crystals, which form the mineral fluorapatite within the bone, especially at sites of bone remodelling. A study currently in progress of publication by our group has shown the ability of [18F]Fluoride PET-CT imaging of bone formation in AS to predict response to anti-TNF treatment.

[18F]Fluoride PET-CT scans visualize bone formation in spondyloarthritis patients

T0, T6, T12 and T24 weeks.