Clinical Research Directory

Clinical Study on the Application of PET Probes Targeting DDR2 in the Diagnosis of Interstitial Lung Disease With Cognitive Impairment

Sponsor: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

Summary

According to statistics, 45% of human disease-related deaths are associated with organ fibrosis, among which pulmonary fibrosis poses a severe threat to patients' lives. In recent years, the application of novel therapeutic approaches (such as tumor immunotherapy and organ transplantation) and COVID-19 infections have further expanded the clinical demand for the diagnosis and treatment of pulmonary fibrosis. Currently, the two small-molecule drugs approved for idiopathic pulmonary fibrosis (IPF) (pirotinib and nintedanib) can only slow the decline in lung function and fail to improve patient mortality . Therefore, early diagnosis and early treatment of pulmonary fibrosis have become a clinical consensus , urgently requiring the emergence of innovative technologies and methods. Recent studies have demonstrated that collagen is not only a product of fibrosis but also a driving factor in its sustained progression . Therefore, identifying key molecular targets that promote collagen-driven fibrotic progression represents a critical direction for anti-fibrotic therapeutic research. Human collagen receptors identified include the discoidin domain receptor (DDR) family (including DDR1 and DDR2) and the integrin family (including α1β1, α2β1, α10β1, and α11β1). Extensive literature and preliminary research by various groups have established that DDR2 is the collagen receptor with the most significantly elevated expression level in the lung tissue of IPF patients. Unlike the "fast-on, fast-off" activation pattern of cytokine receptor tyrosine kinases (RTKs), the tyrosine phosphorylation of DDR1 and DDR2 requires the binding of large ligand molecules such as collagen for several hours before induction and can persist for dozens of hours, exhibiting a unique "slow-on, slow-off" pattern. This activation characteristic suggests that such molecular mechanisms may underlie the enduring biological effects mediated by DDRs in the progression of chronic fibrotic diseases.

Official title: Clinical Study on the Application of Positron Emission Tomography (PET) Probes Targeting DDR2 in the Diagnosis of Interstitial Lung Disease and Interstitial Lung Disease With Cognitive Impairment

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