Background:Bone formation in spondyloarthritis (SpA) is presumably related to local enthesitis/peri-articular inflammation and ultimately may lead to functional limitation (1,2). X-rays only allow long-term monitoring of bone formation (≥2 years) (3). Imaging techniques that can visualize bone formation at an early stage would therefore be valuable. Positron Emission Tomography (PET) using [18F]Fluoride can visualize and quantify (early changes in) bone formation at molecular level (4).Objectives:To investigate the feasibility of [18F]Fluoride to assess new bone formation at axial and peripheral enthesial sites in SpA patients.Methods:Thus far, 5 of the total of 15 patients with clinically active ankylosing spondylitis (AS) (according to modified New York criteria and BASDAI ≥4) and 8 of the 25 patients with active psoriatic arthritis (PsA) (according to CASPAR criteria and ≥1 clinically active enthesitis) were included. Of each patient, a whole body [18F]Fluoride PET-CT scan was performed. All scans were visually judged and scored dichotomously by one reader (blinded for clinical data) for PET-positive lesions in the spine, peripheral enthesis sites and joints. Low dose CT was used for anatomical reference.Results:The study is ongoing, with whole body [18F]Fluoride PET-CT scans available in five AS patients and eight PsA patients. In 4/5 AS scans, at least (≥1) PET positive lesions were found in the cervical, thoracic and/or lumbar vertebrae. These were mainly found in anterior corners of vertebrae and bridging syndesmophytes (Fig. 1A). In all eight PsA patients, at least 1 PET positive lesion was visualized, projected either at the site of a tendon attachment (fascia plantaris, achilles- and patella tendon (Fig 1B)) or peri-articularly (in the ankle or wrist).Fig 1.[18F]Fluoride uptake in the cervical, thoracic and lumbar spine in a clinically active AS patient (A) and in the patella tendon of the right knee in a clinically active PsA patient (B)Conclusion:[18F]Fluoride PET uptake, reflecting new bone formation, can be visualized at heterogeneously distributed enthesis and (peri-)articular sites in AS- and PsA patients. The technique therefore is sensitive to visualize new bone formation and may reflect local disease activity. Additional scans will be collected and analyzed quantitatively, also after anti-TNF or Secukinumab treatment, to further investigate the applicability of [18F]Fluoride PET for monitoring of therapeutic effects on bone formation in SpA.References: :[1]Maksymowych WP, Mallon C, Morrow S, Shojania K, Olszynski WP, Wong RL, et al. Development and validation of the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann Rheum Dis. 2009;68(6):948-53.[2]Rezvani A, Bodur H, Ataman S, Kaya T, Bugdayci DS, Demir SE, et al. Correlations among enthesitis, clinical, radiographic and quality of life parameters in patients with ankylosing spondylitis. Mod Rheumatol. 2014;24(4):651-6.[3]Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum 2005;52:1000-8..[4]Bruijnen ST, Verweij NJF, van Duivenvoorde L, Bravenboer N, Baeten D, van Denderen JC, et al. [18F]Fluoride PET-CT imaging of bone formation in ankylosing spondylitis before and after 12 weeks of anti-TNF treatment. 2017.Acknowledgments:We thank EULAR Foreum, Pfizer and Novartis for financial support of this investigator initiated study.Disclosure of Interests:Jerney de Jongh: None declared, Robert Hemke: None declared, Gerben C.J. Zwezerijnen: None declared, Maqsood Yaqub: None declared, Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Marleen G.H. van de Sande Grant/research support from: Novartis, Eli lily, UCB, Jansen, Consultant of: Abbvie, Novartis, Eli lily, MSD, Arno Van Kuijk: None declared, Irene Bultink: None declared, Lot Burgemeister: None declared, Nancy M.A. van Dillen: None declared, Alexandre Voskuyl: None declared, Conny J. van der Laken: None declared
Synthesis of 2‐(chlorodifluoromethyl)indoles for nucleophilic halogen exchange with [18F]fluoride