VALIDATION OF AN IN VIVO IMAGING MODEL IN MICE TO STUDY THE COLLAGEN-INDUCED ARTHRITIS USING NEAR INFRARED FLUOROPHORE-LABELED 2-DEOXYGLUCOSE

SALINAS, FACUNDO J.; PÉREZ-SÁEZ, J.M.; HOCKL, PABLO F.; SALVETTI, NATALIA R.; ORTEGA, HUGO H.

Mar del Plata

Congreso; Reunion conjunta SAIC SAI SAFIS 2018; 2018

SAIC SAI SAFIS SAV NANOMED-ar

In vivo bioluminescent imaging systems are increasingly being utilizedas a reference method in biomedicine due to its advantages of high sensitivity,non-invasiveness, non-radioactivity and low cost.The effectiveness of optical imaging heavily depends the use ofvalidated models. Rheumatoid arthritis (RA) is a systemic autoimmune diseasethat affects the joint synovium, leading to chronic inflammation, and finallyloss of function. The collagen induced arthritis (CIA) mouse model is inducedby immunization with type II collagen (CII) and it is the most commonly studiedautoimmune model of rheumatoid arthritis. Previous works from our laboratoryhas demonstrated that glucose metabolism is increased in stromal andinfiltrating cells in this arthritis model. Taking into account theseobservations, our aim was to evaluate the biodistribution of 2-deoxyglucose(2-DG) labelled 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. MaleDBA/1 mice (8-10 week old) (n=3) were immunized with CII emulsified in CFA byintradermal injection at the base of the tail. At day 40, when the symptomswere manifested, 20 nmol of IRDye 800CW labeled 2-DG were administered EV. Nonimmunized mice were used as control. The images were acquired at 0, 4,6,12 and24 hs after administration with Pearl Trilogy Image System (LI-CORBiosciences). A specific distribution of 2-DG was observed in arthritic micejoints compared to nonarthritic control mice. The fluorescence was evidencedspecifically in distal limb joints and mandibular area, with a significantdifference in the fluorescence signal (P<0.05) from 4 hs (3.79 +/- 1.48), upto 24 hs (3.55+/-0.91) in relation to basal signaling (0.09+/-0.07). These dataindicate that targeting metabolic pathways is a novel approach to analyzeexperimental models of arthritis.