Prediction of Response to Therapy for Autoimmune/Inflammatory Diseases Using an Activated Macrophage-Targeted Radioimaging Agent.
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 ((99m)Tc-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 (99m)Tc-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.
Department of Chemistry, Purdue University , West Lafayette, Indiana 47907, United States.
Lindsay E
LE
Kelderhouse
Department of Chemistry, Purdue University , West Lafayette, Indiana 47907, United States.
Meridith T
MT
Robins
Department of Chemistry, Purdue University , West Lafayette, Indiana 47907, United States.
Katelyn E
KE
Rosenbalm
Department of Chemistry, Purdue University , West Lafayette, Indiana 47907, United States.
Emily K
EK
Hoylman
Department of Chemistry, Purdue University , West Lafayette, Indiana 47907, United States.
Sakkarapalayam
S
Mahalingam
Department of Chemistry, Purdue University , West Lafayette, Indiana 47907, United States.
Philip S
PS
Low
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy; D050197:Atherosclerosis / Q000188:drug therapy; D001327:Autoimmune Diseases / Q000188:drug therapy*; D003093:Colitis, Ulcerative / Q000188:drug therapy; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D058973:Folate Receptors, GPI-Anchored / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015609:Organotechnetium Compounds / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000188:drug therapy; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D058973:Folate Receptors, GPI-Anchored; D007155:Immunologic Factors; D015609:Organotechnetium Compounds; C000594840:technetium 99m EC20 folate peptide
EC20 radioimaging; activated macrophages; atherosclerosis; folate receptor targeting; idiopathic pulmonary fibrosis; inflammatory and autoimmune diseases; rheumatoid arthritis; ulcerative colitis