title: In-vivo quantitative assessment of the therapeutic response in a mouse model of collagen-induced arthritis using18F-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 of18F-fluorodeoxyglucose positron emission tomography (18F-FDG) as an in-vivo screening tool for anti-inflammatory drugs using the mouse CIA model. The radiotracer18F-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 of18F-FDG with the progression of the disease and a significant decrease in the post-treatment group.18F-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 of18F-FDG PET as a tool for in-vivo drug screening for inflammatory arthritis and to monitor the therapeutic effects in a longitudinal setting.
authors.affiliation: Division of Dermatology, University of California Davis, School of Medicine, Sacramento, CA, USA.
authors.forename: A
authors.identifier: 0000-0003-2385-7325
authors.initials: A
authors.lastname: Mitra
authors.affiliation: Veterans Affairs Medical Center, Mather, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kundu-Raychaudhuri
authors.affiliation: Veterans Affairs Medical Center, Mather, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Abria
authors.affiliation: Veterans Affairs Medical Center, Mather, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rona
authors.affiliation: Department of Radiology, University of California Davis, School of Medicine, Sacramento, CA, USA.|Center for Molecular and Genomic Imaging, University of California Davis, CA, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Chaudhari
authors.affiliation: Veterans Affairs Medical Center, Mather, CA, USA.|Division of Rheumatology, Allergy and Clinical Immunology, University of California Davis, School of Medicine, Davis, CA, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Raychaudhuri
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000276:immunology* / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D003094:Collagen / Q000008:administration & dosage; D004195:Disease Models, Animal; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical / Q000379:methods; D019788:Fluorodeoxyglucose F18; D007596:Joints / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D019275:Radiopharmaceuticals; D014409:Tumor Necrosis Factor-alpha; D019788:Fluorodeoxyglucose F18; D003094:Collagen
keywords: CIA; PET; anti-TNF; inflammation