Validation of an in vivo imaging model in mice to study the collagen-induced arthritis using near infrared fluorophore-labeled 2-deoxyglucose.

HOCKL PF; SALINAS FJ ; SALVETTI NR; PÉREZ SÁEZ JM; ORTEGA HH

Mar del Plata

Congreso; LXIII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC), LXVI Reunión anual de la SAI; Reunión anual de la SAFIS; con la participación de la SAV y Asociacion Argentina de Nanomedicinas (NANOMEDAR); 2018

SAIC

In vivo bioluminescent imaging systems are increasingly being utilized as a reference method in biomedicine due to its advantages of high sensitivity, non-invasiveness, no radioactivity, and low cost. The effectiveness of optical imaging heavily depends the use of validated models. Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects the joint synovium, leading to chronic inflammation, and finally loss of function. The collagen-induced arthritis (CIA) mouse model is induced by immunization with type II collagen (CII) and it is the most commonly studied autoimmune model of rheumatoidarthritis. Previous works from our laboratory has demonstrated that glucose metabolism is increased in stromal and infiltrating cells in this arthritis model. Taking into account these observations, our aim was to evaluate the biodistribution of 2-deoxyglucose (2-DG)labeled with a NIR fluorophore for in vivo optical imaging in mice. 2-DG is a glucose analog that utilizes the GLUT transporters and upon phosphorylation, it is not metabolized further and is effectively trapped within the cell. Male DBA/1 mice (8?12 wk old) (n=3) were immunized with CII emulsified in CFA by intradermal injection at the base of the tail. At day 40 when the symptoms were manifested, 20nmol of IRDye 800CW labeled 2-DG were administrated EV. Non-immunized mice were used as control. The images were acquired at 0, 4, 6, 12 and 24 h after administration with a Pearl Trilogy Image System (LI-COR Biosciences). A specific distribution of 2-DG was observed in arthritic mice joints compared to nonarthritic control mice. The fluorescence was evidenced specifically in distal limb joints and mandibular area, with a significant difference in the fluorescencesignal (p< 0.05) from 4 hours (3.79+/-1.48), up to 24 hours (3.55+/-0.91) in relation to basal signaling (0.09+/-0.07). These data indicate that targeting metabolic pathways is a novel approach to analyze experimental models of arthritis.