In-vivo quantitative assessment of the therapeutic response in a mouse model of collagen-induced arthritis using 18 F-fluorodeoxyglucose positron emission tomography.

Abstract

Mouse collagen-induced arthritis (CIA) is the most commonly used animal model to investigate underlying pathogenesis of autoimmune arthritis and to demonstrate the therapeutic efficacy of novel drugs in autoimmune arthritis. The conventional read-outs of CIA are clinical score and histopathology, which have several limitations, including (i) subjected to observer bias; and (ii) longitudinal therapeutic efficacy of a new drug cannot be determined. Thus, a robust, non-invasive, in-vivo drug screening tool is currently an unmet need. Here we have assessed the utility of 18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG) as an in-vivo screening tool for anti-inflammatory drugs using the mouse CIA model. The radiotracer 18 F-FDG and a PET scanner were employed to monitor CIA disease activity before and after murine anti-tumour necrosis factor (TNF)-α antibody (CNTO5048) therapy in the mouse CIA model. Radiotracer concentration was derived from PET images for individual limb joints and on a per-limb basis, and Spearman's correlation coefficient (ρ) was determined with clinical score and histology of the affected limbs. CNTO5048 improved arthritis efficiently, as evidenced by clinical score and histopathology. PET showed an increased uptake of 18 F-FDG with the progression of the disease and a significant decrease in the post-treatment group. 18 F-FDG uptake patterns showed a strong correlation with clinical score (ρ=0·71, P < 0·05) and histopathology (ρ=0·76, P < 0·05). This study demonstrates the potential of 18 F-FDG PET as a tool for in-vivo drug screening for inflammatory arthritis and to monitor the therapeutic effects in a longitudinal setting.