Background: Rheumatoid Arthritis (RA) is one of the most common rheumatic diseases. Joint inflammation and pathological growth of joint cartilage causes swollen, painful joints, which severely diminishes the patients' life quality. There is no causal treatment. Symptomatic therapies should start as early as possible to take maximal effect. Hence, diagnostic procedures capable of detecting affected joints before the onset of clinical symptoms are highly desirable. We explored the value of PETimaging of integrin subtypes αvβ3 and α5β1 for early detection of RA foci in collagen-induced arthritis (CIA) mouse models.
Results: Development of RA in CIA mice was monitored by paw scoring, and αvβ3- and α5β1- integrin expression was quantified by µPET using 68Ga-Avebetrin and 68Ga-Aquibeprin. For consecutive sections of selected decalcified joints (knee, ankle), arthritic degeneration and integrin expression were assessed by MOVAT staining and β3/α5 immunohistochemistry (IHC), respectively. β3- and α5-IHC revealed elevated levels of both αvβ3- and α5β1-integrin in arthritic joints. Unlike αvβ3, α5β1 is strongly expressed in the proliferating synovial lining layer, which suggests that its presence is directly related to RA development. For mice with advanced RA (6 weeks after CIA), PET signals for α5β1-integrin were substantially stronger (>300% of baseline) than that of αvβ3-integrin (<200%). A longitudinal PET follow-up revealed that the manifestation of clinical symptoms of RA is preceded by upregulation of α5β1- but not of αvβ3-integrin.
Conclusion: α5β1-integrin PET could add a new functional imaging aspect to the portfolio of RA diagnostics because it appears to be a specific biomarker for early RA development. We propose α5β1-integrin PET as a valuable tool to achieve a higher precision for early diagnosis of RA, including initial staging, monitoring of the disease course and drug treatment, and for planning of radiosynoviorthesis (RSO).
Keywords: Rheumatoid arthritis; Positron emission tomograph; Integrins; Animal models; Collagen induced arthritis; Immunohistochemistry