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Sci Rep. 2016 Jan 22;6:19755. doi: 10.1038/srep19755.

Non-invasive Imaging of Idiopathic Pulmonary Fibrosis Using Cathepsin Protease Probes.

Author information

1
Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305 USA.
2
Department of Radiology, Stanford University School of Medicine, Stanford, CA 94305 USA.
3
Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305 USA.
4
Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, CA 94305 USA.
5
Department of Pulmonary and Critical Care Medicine, Stanford University School of Medicine, Stanford, CA 94305 USA.
6
Department of Nuclear Medicine, Beijing, 100730, China.
7
Respiratory Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Science &Peking Union Medical College, Beijing, 100730, China.
8
Department of Medicine, University of California San Francisco, San Francisco, CA 94143 USA.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a lethal, chronic, progressive disease characterized by formation of scar tissue within the lungs. Because it is a disease of unknown etiology, it is difficult to diagnose, to predict disease course and to devise treatment strategies. Recent evidence suggests that activated macrophages play key roles in the pathology of IPF. Therefore, imaging probes that specifically recognize these pools of activated immune cells could provide valuable information about how these cells contribute to the pathobiology of the disease. Here we demonstrate that cysteine cathepsin-targeted imaging probes can be used to monitor the contribution of macrophages to fibrotic disease progression in the bleomycin-induced murine model of pulmonary fibrosis. Furthermore, we show that the probes highlight regions of macrophage involvement in fibrosis in human biopsy tissues from IPF patients. Finally, we present first-in-human results demonstrating non-invasive imaging of active cathepsins in fibrotic lesions of patients with IPF. Together, our findings validate small molecule cysteine cathepsin probes for clinical PET imaging and suggest that they have the potential to be used to generate mechanistically-informative molecular information regarding cellular drivers of IPF disease severity and progression.

PMID:
26797565
PMCID:
PMC4726431
DOI:
10.1038/srep19755
[Indexed for MEDLINE]
Free PMC Article

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