Vanderbilt researchers have received an R01 grant from the National Institutes of Health to study a novel non-invasive imaging approach to detect activation of inflammatory cells in the lungs of patients with chronic obstructive pulmonary disease (COPD), a progressive lung condition that makes breathing difficult.
Timothy Blackwell, M.D., and H. Charles Manning, Ph.D., will be the principal investigators for the grant, partnering with Pierre Massion, M.D., who is studying the early detection of lung cancer in high risk populations, including patients with COPD.
Capitalizing on prior work in which they developed an imaging probe for use in animal models to identify activated macrophages, the investigators have now developed a probe for PET imaging of activated macrophages in the lungs of humans, said Blackwell, Ralph and Lulu Owen Professor of Medicine and director of the Division of Allergy, Pulmonary and Critical Care.
Macrophages provide the first line of host defense against invaders in the lungs by patrolling the airways, devouring particulates and microbes, and activating the inflammatory cascade when necessary.
“Persistent macrophage activation plays a key role in the development of multiple inflammatory lung diseases, including COPD,” Blackwell said. “Studying this cell population in humans is complicated by the invasive methods currently required to obtain sufficient quantities of cells. Non-invasive imaging of activated macrophages would allow frequent monitoring of disease progression and response to therapy.”
In previously published studies, investigators focused on developing imaging strategies based on expression of folate receptor (FR) by activated macrophages. FRβ expression and folate uptake by macrophages increase with lung inflammation. They used a fluorescent probe for in vivo molecular imaging and showed that this probe binds selectively to activated macrophages and monocytes.
In this proposal, the team will test the hypothesis that folate-based molecular imaging using PET to detect activated macrophages can identify patients with COPD and determine those most likely to have rapid disease progression due to higher levels of chronic lung inflammation.
“These studies will determine whether folate-based imaging is useful for quantifying inflammation in lung diseases like COPD, and whether identifying macrophage activation could delineate a subgroup of patients who would benefit from anti-inflammatory or macrophage-targeted therapies,” Blackwell said.
This research is supported by a grant from the National Heart, Lung and Blood Institute (1R01HL131906-01).
