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 language | English (US) |
|---|---|
| Pages (from-to) | 3547-3555 |
| Number of pages | 9 |
| Journal | Molecular pharmaceutics |
| Volume | 12 |
| Issue number | 10 |
| DOIs | |
| State | Published - 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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