In vivo assessments of mucus dynamics in the rat lung using a Gd‐Cy5.5‐bilabeled contrast agent for magnetic resonance and optical imaging

Abstract

Dysfunctions in mucociliary clearance are associated with the accelerated loss of lung function in several respiratory diseases. Approaches enabling the in vivo visualization of mucus dynamics in rodents at high resolution and sensitivity would be beneficial for experimental lung research. We describe the synthesis and characterization of two bilabeled amino dextranbased probes binding specifically to mucin. Labeling of secreted mucus and of mucin in goblet cells in the lungs of lipopolysaccharide-challenged rats has been demonstrated in vivo with near-infrared fluorescence and MRI and confirmed by histology. The effects of uridine triphosphate were then studied in lipopolysaccharide-challenged rats by simultaneously administering the imaging probe and the compound. The data suggest that uridine triphosphate increased the mucociliary clearance, but at the same time induced a release of mucin from goblet cells, thus not contributing to the overall reduction of mucus in the lung. The approach outlined here enables one to derive information on mucus clearance, as well as secretion. Such a global view on mucus dynamics may prove invaluable when testing new pharmacological agents aimed at improving mucociliary clearance.

A View on Imaging in Drug Research and Development for Respiratory Diseases

“…MRI can detect secreted mucus in the lungs of spontaneously respiring rats up to 8 days after a single LPS challenge Tigani et al, 2002). Bilabeled amino dextran-based probes binding specifically to mucus have been synthesized to extract information on mucus dynamics in this model (Blé et al, 2009b). …”

Targeted imaging of brain gliomas using multifunctional Fe3O4/MnO nanoparticles

“…[1][2][3][4][5] However, single mode (T 1 or T 2 ) contrast agents are not always sufficient to provide highly accurate diagnostic information. Therefore, contrast agents with T 1 and T 2 dual modes have been developed for an improved diagnosis.…”

“…The T 1 positive and T 2 negative contrast agents are used in the clinic to improve the sensitivity of magnetic resonance imaging (MRI) by increasing the contrast of the tumor tissue from the normal tissue. [1][2][3][4][5] However, single mode (T 1 or T 2 ) contrast agents are not always sufficient to provide highly accurate diagnostic information. Therefore, contrast agents with T 1 and T 2 dual modes have been developed for an improved diagnosis.…”