TY - JOUR
T1 - Predicting Response to Therapy for Autoimmune and Inflammatory Diseases Using a Folate Receptor-Targeted Near-Infrared Fluorescent Imaging Agent
AU - Kelderhouse, Lindsay E.
AU - Mahalingam, Sakkarapalayam
AU - Low, Philip S.
N1 - Funding Information:
This work was supported by a research grant from On Target Laboratories, LLC.
Publisher Copyright:
© 2015, World Molecular Imaging Society.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Activated macrophages
KW - Atherosclerosis imaging
KW - Fluorescence imaging of autoimmune disease
KW - Folate receptor targeting
KW - Idiopathic pulmonary fibrosis imaging
KW - Inflammatory and autoimmune diseases
KW - Near-infrared fluorescent dye
KW - Rheumatoid arthritis imaging
KW - Ulcerative colitis imaging
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U2 - 10.1007/s11307-015-0876-y
DO - 10.1007/s11307-015-0876-y
M3 - Article
C2 - 26242480
AN - SCOPUS:84959907161
VL - 18
SP - 201
EP - 208
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
SN - 1536-1632
IS - 2
ER -