title: Predicting Response to Therapy for Autoimmune and Inflammatory Diseases Using a Folate Receptor-Targeted Near-Infrared Fluorescent Imaging Agent.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  OTL0038 has the ability to predict responses to multiple therapies in four murine models of inflammation.
authors.affiliation: Department of Chemistry, Purdue University, 720 Clinic Drive, West Lafayette, IN, 47907, USA.
authors.forename: Lindsay E
authors.initials: LE
authors.lastname: Kelderhouse
authors.affiliation: Department of Chemistry, Purdue University, 720 Clinic Drive, West Lafayette, IN, 47907, USA.
authors.forename: Sakkarapalayam
authors.initials: S
authors.lastname: Mahalingam
authors.affiliation: Department of Chemistry, Purdue University, 720 Clinic Drive, West Lafayette, IN, 47907, USA. plow@purdue.edu.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000473:pathology / Q000628:therapy; D050197:Atherosclerosis / Q000150:complications / Q000473:pathology / Q000628:therapy; D001327:Autoimmune Diseases / Q000150:complications / Q000473:pathology / Q000628:therapy*; D002417:Cattle; D003093:Colitis, Ulcerative / Q000150:complications / Q000473:pathology / Q000628:therapy; D003106:Colon / Q000473:pathology; D005260:Female; D005453:Fluorescence; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism*; D007249:Inflammation / Q000150:complications / Q000473:pathology / Q000628:therapy*; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D057054:Molecular Imaging / Q000379:methods*; D011658:Pulmonary Fibrosis / Q000150:complications / Q000473:pathology / Q000628:therapy; D016896:Treatment Outcome
chemical_list: D058973:Folate Receptors, GPI-Anchored
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