Oral and Subcutaneous Administration of a Near-Infrared Fluorescent Molecular Imaging Agent Detects Inflammation in a Mouse Model of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that causes irreversible damage to the joints. However, effective drugs exist that can stop disease progression, leading to intense interest in early detection and treatment monitoring to improve patient outcomes. Imaging approaches have the potential for early detection, but current methods lack sensitivity and/or are time-consuming and expensive. We examined potential routes for self-administration of molecular imaging agents in the form of subcutaneous and oral delivery of an integrin binding near-infrared (NIR) fluorescent imaging agent in an animal model of RA with the long-term goal of increasing safety and patient compliance for screening. NIR imaging has relatively low cost, uses non-ionizing radiation, and provides minimally invasive spatial and molecular information. This proof-of-principle study shows significant uptake of an IRDye800CW agent in inflamed joints of a collagen antibody induced arthritis (CAIA) mouse model compared to healthy joints, irrespective of the method of administration. The imaging results were extrapolated to clinical depths in silico using a 3D COMSOL model of NIR fluorescence imaging in a human hand to examine imaging feasability. With target to background concentration ratios greater than 5.5, which are achieved in the mouse model, these probes have the potential to identify arthritic joints following oral delivery at clinically relevant depths.