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Predicting Response to Therapy for Autoimmune and Inflammatory Diseases Using a Folate Receptor-Targeted Near-Infrared Fluorescent Imaging Agent

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Abstract

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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Acknowledgments

This work was supported by a research grant from On Target Laboratories, LLC.

Conflict of Interest

PSL is a board member, significant shareholder, and Chief Science Officer of On Target Laboratories LLC, which was incorporated in 2010. All other authors declare no competing interests.

Authors’ contributions

LEK designed the study, performed the experiments, analyzed the data, and wrote the manuscript. SM synthesized the OTL0038. PSL conceived and supervised the study as well as reviewed the manuscript.

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Authors and Affiliations

  1. Department of Chemistry, Purdue University, 720 Clinic Drive, West Lafayette, IN, 47907, USA

    Lindsay E. Kelderhouse, Sakkarapalayam Mahalingam & Philip S. Low

Authors
  1. Lindsay E. Kelderhouse
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  2. Sakkarapalayam Mahalingam
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  3. Philip S. Low
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Corresponding author

Correspondence to Philip S. Low.

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Kelderhouse, L.E., Mahalingam, S. & Low, P.S. Predicting Response to Therapy for Autoimmune and Inflammatory Diseases Using a Folate Receptor-Targeted Near-Infrared Fluorescent Imaging Agent. Mol Imaging Biol 18, 201–208 (2016). https://doi.org/10.1007/s11307-015-0876-y

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  • DOI: https://doi.org/10.1007/s11307-015-0876-y

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