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Fluorescence-mediated Tomography for the Detection and Quantification of Macrophage-related Murine Intestinal Inflammation
Published on: December 15, 2017
Predicting Response to Therapy for Autoimmune and Inflammatory Diseases Using a Folate Receptor-Targeted
Lindsay E Kelderhouse1, Sakkarapalayam Mahalingam1, Philip S Low2
1Department of Chemistry, Purdue University, 720 Clinic Drive, West Lafayette, IN, 47907, USA.
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.
Insights
A novel dye, OTL0038, can predict treatment response in inflammatory diseases. This near-infrared dye accumulates in inflamed tissues, indicating therapeutic efficacy in animal models.
Area of Science:
- Immunology
- Medical Imaging
- Pharmacology
Background:
- Current therapies for inflammatory and autoimmune diseases show variable patient responses.
- Identifying non-responders early is crucial to prevent disease progression and reduce healthcare costs.
Purpose of the Study:
- To evaluate the utility of OTL0038, a folate receptor-targeted near-infrared dye, in predicting therapeutic responses.
- To assess OTL0038's efficacy across diverse inflammatory disease models.
Main Methods:
- Four murine models of inflammatory disease were established (rheumatoid arthritis, ulcerative colitis, pulmonary fibrosis, atherosclerosis).
- Mice received anti-inflammatory treatments and were injected with OTL0038.
- OTL0038 uptake in inflamed lesions was correlated with clinical disease severity.
Main Results:
- OTL0038 demonstrated accumulation at inflammation sites in all four disease models.
- Changes in OTL0038 uptake in lesions preceded clinical symptom changes.
- This predictive capability was observed across all tested anti-inflammatory drugs.
Conclusions:
- OTL0038 serves as a reliable predictor of therapeutic response in multiple inflammatory conditions.
- The dye's ability to detect early treatment effects offers a potential tool for personalized medicine in autoimmune diseases.
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