In vivoquantification of mouse autoimmune arthritis by PET/CT

Abstract

Aim To quantify the progression and severity of mouse collagen-induced arthritis (CIA) using an in vivo imaging tool, 18F-fluorodeoxyglucose (18F-FDG) PET/CT, and validate it against gold standard ‘histopathological’ evaluation. Method The PET radiotracer 18F-FDG, a marker for glucose metabolism, was injected in mice at different stages during the development of CIA and the radiotracer distribution was imaged using a PET scanner. A sequential CT scan provided correlated anatomy. Radiotracer concentration was derived from PET/CT images for individual limb joints and on a per-limb basis at different stages of the disease. The imaging outcomes were subjected to correlation analysis with concurrently-measured clinical and histological score. Results Clinical and histological score, and hence disease severity, showed a strong linear correlation (R2=0.71, p=0.001, and R2=0.87, p<0.001, respectively) with radiotracer concentration measured from PET/CT during the progression of CIA. Conclusions The strong positive correlation of the 18F-FDG PET/CT findings with the histopathological evaluation at different stages of the disease suggest the potential of this imaging tool for the non-invasive assessment of progression and severity in mouse autoimmune arthritis. Thus, 18F-FDG PET/CT can be considered as a non invasive tool in preclinical studies for development of novel therapies of inflammatory arthritis.

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

“…This result was in concordance with our earlier study [5], albeit that study was performed in a small number of animals. PS was determined to have a median value of 1Á02 (range 5 0Á85-1Á05) on day 0.…”

“…Arthritis was induced (n 5 30) using type II bovine collagen (CII) [5,8,10] in eight-week-old arthritissusceptible male/1J mice (Jackson Laboratory, ME, USA). Arthritis was induced (n 5 30) using type II bovine collagen (CII) [5,8,10] in eight-week-old arthritissusceptible male/1J mice (Jackson Laboratory, ME, USA).…”

“…Before PET scan, the severity of the arthritis was scored using clinical score for each limb, as described in an earlier report [5]. Due to the asymmetrical nature of the disease, CS of the most inflamed joint in each animal was considered for statistical analysis.…”

“…Subsequently, tissue sections were made and stained with haematoxylin and eosin (H&E) to evaluate the severity of the inflammatory infiltrates, which was graded on a scale of 0-3, where 0 5 normal, 1 5 mild, 2 5 moderate and 3 5 severe [5]. Limbs were dissected and processed in 10% formalin followed by decalcification.…”

Monitoring Therapy Response of Experimental Arthritis with Radiolabeled Tracers Targeting Fibroblasts, Macrophages, or Integrin αvβ3

“…Despite the fact that 18 F-FDG was suggested as a good tool to develop the therapeutic effect of novel therapies of inflammatory arthritis in the study by Kundu-Raychaudhuri et al (42), in a preclinical model Laverman et al showed that 18 F-FDG was inferior to other nuclear imaging tracers when correlating uptake of 18 F-FDG with arthritis score (8).…”