Prediction of response to therapy for autoimmune/inflammatory diseases using an activated macrophage-Targeted radioimaging agent

Lindsay E. Kelderhouse, Meridith T. Robins, Katelyn E. Rosenbalm, Emily K. Hoylman, Sakkarapalayam Mahalingam, Philip S. Low

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3547-3555
Number of pages9
JournalMolecular pharmaceutics
Volume12
Issue number10
DOIs
StatePublished - Oct 5 2015

Keywords

  • Activated macrophages
  • Atherosclerosis
  • EC20 radioimaging
  • Folate receptor targeting
  • Idiopathic pulmonary fibrosis
  • Inflammatory and autoimmune diseases
  • Rheumatoid arthritis
  • Ulcerative colitis

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

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