Visualizing arthritic inflammation and therapeutic response by fluorine-19 magnetic resonance imaging (19F MRI)

Background: Non-invasive imaging of inflammation to measure the progression of autoimmune diseases, such as rheumatoid arthritis (RA), and to monitor responses to therapy is critically needed. V-Sense, a perfluorocarbon (PFC) contrast agent that preferentially labels inflammatory cells, which are then recruited out of systemic circulation to sites of inflammation, enables detection by F-19 MRI. With no F-19 background in the host, detection is highly-specific and can act as a proxy biomarker of the degree of inflammation present. Methods: Collagen-induced arthritis in rats, a model with many similarities to human RA, was used to study the ability of the PFC contrast agent to reveal the accumulation of inflammation over time using F-19 MRI. Disease progression in the rat hind limbs was monitored by caliper measurements and F-19 MRI on days 15, 22 and 29, including the height of clinically symptomatic disease. Naive rats served as controls. The capacity of the PFC contrast agent and F-19 MRI to assess the effectiveness of therapy was studied in a cohort of rats administered oral prednisolone on days 14 to 28. Results: Quantification of F-19 signal measured by MRI in affected limbs was linearly correlated with disease severity. In animals with progressive disease, increases in F-19 signal reflected the ongoing recruitment of inflammatory cells to the site, while no increase in F-19 signal was observed in animals receiving treatment which resulted in clinical resolution of disease. Conclusion: These results indicate that F-19 MRI may be used to quantitatively and qualitatively evaluate longitudinal responses to a therapeutic regimen, while additionally revealing the recruitment of monocytic cells involved in the inflammatory process to the anatomical site. This study may support the use of F-19 MRI to clinically quantify and monitor the severity of inflammation, and to assess the effectiveness of treatments in RA and other diseases with an inflammatory component.