Journal
MOLECULAR IMAGING AND BIOLOGY
Volume 18, Issue 2, Pages 201-208Publisher
SPRINGER
DOI: 10.1007/s11307-015-0876-y
Keywords
Inflammatory and autoimmune diseases; Folate receptor targeting; Activated macrophages; Near-infrared fluorescent dye; Fluorescence imaging of autoimmune disease; Idiopathic pulmonary fibrosis imaging; Rheumatoid arthritis imaging; Ulcerative colitis imaging; Atherosclerosis imaging
Funding
- On Target Laboratories, LLC
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Purpose: Although current therapies for many inflammatory/autoimmune diseases are effective, a significant number of patients still exhibit only partial or negligible responses to therapeutic intervention. Since prolonged use of an inadequate therapy can result in both progressive tissue damage and unnecessary expense, methods to identify nonresponding patients are necessary. Procedures: Four murine models of inflammatory disease (rheumatoid arthritis, ulcerative colitis, pulmonary fibrosis, and atherosclerosis) were induced, treated with anti-inflammatory agents, and evaluated for inflammatory response. The mice were also injected intraperitoneally with OTL0038, a folate receptor-targeted near-infrared dye that accumulates in activated macrophages at sites of inflammation. Uptake of OTL0038 in inflamed lesions was then correlated with clinical measurements of disease severity. Results: OTL0038 accumulated at sites of inflammation in all four animal models. More importantly, changes in lesion-associated OTL0038 preceded changes in clinical symptoms in mice treated with all anti-inflammatory drugs examined. Conclusion: OTL0038 has the ability to predict responses to multiple therapies in four murine models of inflammation.
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