Imaging Matrix Remodeling in Pulmonary Fibrosis
Abstract
FY20 PRMRP Topic Area: Pulmonary Fibrosis Area of encouragement: • Development and/or validation of improved tools and animal models (excluding mice) to study pulmonary fibrosis and evaluate therapeutics. Pulmonary fibrosis affects a growing number of subjects in the US. Idiopathic pulmonary fibrosis is a lethal disease with no cure, but for which new therapies are emerging. Currently, it is not clear how these drugs can be best utilized and which patients might benefit from them. The diagnosis of pulmonary fibrosis is based on a number of tests, including in some cases, lung biopsy, which is an invasive procedure and can be associated with major complications, Current imaging modalities, like chest radiography, computed tomography (CT), and magnetic resonance imaging (MRI) provide a snapshot of the lung structure at a given point, without providing any information on disease activity, which is arguably the target of therapeutic interventions to prevent progression and promote regression of fibrosis. In addition, there is some delay before the effect of therapeutic interventions is reflected on the lung structure, and hence becomes detectable by CT and MRI. Accordingly, novel tools are needed to quantify and characterize fibrosis, select the patients for emerging therapies, track the effect of therapeutic interventions to guide the timing of initiation and discontinuation, and improve prognostication. To address these gaps, we seek to develop a new radiotracer for high sensitivity nuclear imaging of pulmonary fibrosis by targeting changes in the structure of collagen that occur during the development and resolution of fibrosis, evaluate this tracer in an established mouse model of pulmonary fibrosis, and evaluate its performance for detecting early changes that occur during resolution of fibrosis in comparison with a standard approach. These studies will help distinguish between established disease and ongoing changes in the lung molecular composition that accompany active or resolving disease. The development, validation, and ultimately clinical translation of these studies will facilitate the monitoring of fibrosis and response to therapeutic interventions, not only in the lung, but also potentially other organs. This will help advance basic research in pulmonary fibrosis and facilitate the development and evaluation of new therapies, and improve the patients’ outcome in the long term.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110083
Entities
People
- Mehran M Sadeghi
Organizations
- United States Army
- Yale University