Abstract

IntroductionRheumatoid arthritis (RA) is a chronic disease, affecting 0.5 to 1% of adults in industrialized countries, in which systemic inflammation and synovitis drive joint destruction. [18F]DPA-714 is a specific tracer of the 18 kDa translocator protein (TSPO), which is overexpressed on activated macrophages, and proposed as a biomarker of neuroinflammation. Today, diagnosis of patients with early inflammatory arthritis is limited by poor sensitivity and specificity. The present study aims to investigate the potential of [18F]DPA-714 to monitor in vivo inflammatory processes at a preclinical stage via positron emission tomography (PET).MethodsRA was induced in Dark Agouti rats by subcutaneous injection of inactivated Mycobacterium tuberculosis. Development of arthritis clinical signs was investigated daily and the severity of the disease evaluated. Animals were imaged at the peak of inflammation using [18F]DPA-714 and a small-animal PET-CT tomograph.ResultsThe first clinical signs appeared at 10 days post-injection, with a peak of inflammation at 20 days. At this time, PET-analyses showed a clear uptake of [18F]DPA-714 in swollen ankles, with mean values of 0.52 ± 0.18% injected dose (ID/cc) for treated (n = 11) and 0.19 ± 0.09 for non-treated (n = 6) rats. A good correlation between [18F]DPA-714’s uptake and swelling was also found. Immunohistochemistry showed an enhanced TSPO expression in hind paws, mainly co-localized with the macrophages specific antigen CD68 expressing cells.ConclusionThese preliminary results demonstrate that the TSPO 18kDa specific radioligand [18F]DPA-714 is adapted for the study and follow-up of inflammation linked to RA in our experimental model, suggesting also a strong potential for clinical imaging of peripheral inflammation.

Highlights

  • Rheumatoid arthritis (RA) is a chronic disease, affecting 0.5 to 1% of adults in industrialized countries, in which systemic inflammation and synovitis drive joint destruction. [18F]DPA-714 is a specific tracer of the 18 kDa translocator protein (TSPO), which is overexpressed on activated macrophages, and proposed as a biomarker of neuroinflammation

  • The present study aims to investigate the potential of [18F]DPA-714 positron emission tomography (PET) to image and quantify in vivo peripheral inflammation in an autoimmune adjuvant-induced RA rat model

  • Rheumatoid arthritis model An arthritic model was induced by a single dose injection of 0.5 mg of Mycobacterium tuberculosis H37 Ra (Mtb) in male Dark Agouti rats (DA rats)

Read more

Summary

Introduction

Rheumatoid arthritis (RA) is a chronic disease, affecting 0.5 to 1% of adults in industrialized countries, in which systemic inflammation and synovitis drive joint destruction. [18F]DPA-714 is a specific tracer of the 18 kDa translocator protein (TSPO), which is overexpressed on activated macrophages, and proposed as a biomarker of neuroinflammation. Rheumatoid arthritis (RA) is a chronic disease, affecting 0.5 to 1% of adults in industrialized countries, in which systemic inflammation and synovitis drive joint destruction. Diagnosis of patients with early inflammatory arthritis is limited by poor sensitivity and specificity. Rheumatoid arthritis (RA) is a chronic inflammatory disorder that can affect many tissues and organs. This disease leads to progressive joint destruction principally due to synovial inflammation, and to articular complications and functional disability. RA is a systemic autoimmune disease that leads to many disorders in organ systems and is associated with other diseases, including infections, malignancies and cardiovascular diseases. Other potential risks, including alcohol abuse, vitamin D status, contraception use and coffee intake, have been reported too [2]

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call