TY - JOUR
T1 - Prediction of response to therapy for autoimmune/inflammatory diseases using an activated macrophage-Targeted radioimaging agent
AU - Kelderhouse, Lindsay E.
AU - Robins, Meridith T.
AU - Rosenbalm, Katelyn E.
AU - Hoylman, Emily K.
AU - Mahalingam, Sakkarapalayam
AU - Low, Philip S.
PY - 2015/10/5
Y1 - 2015/10/5
N2 - The ability to select patients who will respond to therapy is especially acute for autoimmune/inflammatory diseases, where the costs of therapies can be high and the progressive damage associated with ineffective treatments can be irreversible. In this article we describe a clinical test that will rapidly predict the response of patients with an autoimmune/inflammatory disease to many commonly employed therapies. This test involves quantitative assessment of uptake of a folate receptor-Targeted radioimaging agent (99mTc-EC20) by a subset of inflammatory macrophages that accumulate at sites of inflammation. Murine models of four representative inflammatory diseases (rheumatoid arthritis, inflammatory bowel disease, pulmonary fibrosis, and atherosclerosis) show markedly decreased uptake of 99mTc-EC20 in inflamed lesions upon initiation of successful therapies, but no decrease in uptake upon administration of ineffective therapies, in both cases long before changes in clinical symptoms can be detected. This predictive capability should reduce costs and minimize morbidities associated with failed autoimmune/ inflammatory disease therapies.
AB - The ability to select patients who will respond to therapy is especially acute for autoimmune/inflammatory diseases, where the costs of therapies can be high and the progressive damage associated with ineffective treatments can be irreversible. In this article we describe a clinical test that will rapidly predict the response of patients with an autoimmune/inflammatory disease to many commonly employed therapies. This test involves quantitative assessment of uptake of a folate receptor-Targeted radioimaging agent (99mTc-EC20) by a subset of inflammatory macrophages that accumulate at sites of inflammation. Murine models of four representative inflammatory diseases (rheumatoid arthritis, inflammatory bowel disease, pulmonary fibrosis, and atherosclerosis) show markedly decreased uptake of 99mTc-EC20 in inflamed lesions upon initiation of successful therapies, but no decrease in uptake upon administration of ineffective therapies, in both cases long before changes in clinical symptoms can be detected. This predictive capability should reduce costs and minimize morbidities associated with failed autoimmune/ inflammatory disease therapies.
KW - Activated macrophages
KW - Atherosclerosis
KW - EC20 radioimaging
KW - Folate receptor targeting
KW - Idiopathic pulmonary fibrosis
KW - Inflammatory and autoimmune diseases
KW - Rheumatoid arthritis
KW - Ulcerative colitis
UR - http://www.scopus.com/inward/record.url?scp=84986579088&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84986579088&partnerID=8YFLogxK
U2 - 10.1021/acs.molpharmaceut.5b00134
DO - 10.1021/acs.molpharmaceut.5b00134
M3 - Article
C2 - 26333010
AN - SCOPUS:84986579088
VL - 12
SP - 3547
EP - 3555
JO - Molecular pharmaceutics
JF - Molecular pharmaceutics
SN - 1543-8384
IS - 10
ER -