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

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

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)201-208
Number of pages8
JournalMolecular Imaging and Biology
Volume18
Issue number2
DOIs
StatePublished - Apr 1 2016

Keywords

  • Activated macrophages
  • Atherosclerosis imaging
  • Fluorescence imaging of autoimmune disease
  • Folate receptor targeting
  • Idiopathic pulmonary fibrosis imaging
  • Inflammatory and autoimmune diseases
  • Near-infrared fluorescent dye
  • Rheumatoid arthritis imaging
  • Ulcerative colitis imaging

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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