[18F]DPA-714 as a biomarker for positron emission tomography imaging of rheumatoid arthritis in an animal model

Abstract

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. 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).

Methods: RA 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.

Results: The 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.

Conclusion: These 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.