MR imaging, targeting and characterization of pulmonary fibrosis using intra‐tracheal administration of gadolinium‐based nanoparticles

Abstract

Idiopathic pulmonary fibrosis is a devastating disease. Animal models are critical to develop new diagnostic approaches. We investigate here whether the application of an ultra-short echo time MRI sequence combined with the intra-tracheal administration of Gd-based nanoparticles can help to visualize and characterize pulmonary fibrosis in mice. 21 mice were imaged. Treated mice were administered bleomycin. MRI was used for longitudinal detection of bleomycin-induced lung injury from Day 1 up to Day 60. On Day 30, all mice received nanoparticles and MR images were acquired. A signal enhancement of 120% and 50% in fibrotic lesions and healthy tissues respectively was obtained. A twofold increase of contrast-to-noise ratio between fibrotic and healthy tissue was also observed, leading to a more accurate delineation of the extent of fibrosis. The elimination time constant of the nanoparticles was 54% higher in fibrotic lesions. Bleomycin-induced lung injury can be monitored using MRI. Intra-tracheal administration of Gd-based nanoparticles enabled us to enhance fibrotic tissue in lungs but also to extract imaging biomarkers that quantify elimination and diffusion of contrast agents and can characterize fibrotic tissue. The added value of MRI associated with pulmonary administration of contrast agents is key to better understand the lung fibrotic process and monitor drug response in pre-clinical studies, which will be valuable for translational applications. Copyright © 2016 John Wiley & Sons, Ltd.

<p>Nebulised Gadolinium-Based Nanoparticles for a Multimodal Approach: Quantitative and Qualitative Lung Distribution Using Magnetic Resonance and Scintigraphy Imaging in Isolated Ventilated Porcine Lungs</p>

“…Considering the favourable kinetics of these nanoparticles in the lungs (residence time in the order of 1 hour in the lung tissue) followed by an effective and complete renal clearance, several animal models of lung disease were then investigated. For instance, Tassali et al 39 investigated the application of lung MRI protocol combined with the intratracheal administration of the SRP in a bleomycin-induced fibrotic mouse model. The authors reported an MRI signal enhancement of 120% in fibrotic lesions as compared to 50% in healthy tissues and a twofold increase of contrast-to-noise ratio between fibrotic and healthy tissue.…”

Combinatorial treatment of idiopathic pulmonary fibrosis using nanoparticles with prostaglandin E and siRNA(s)

“…NLC were developed by nanostructuring the lipid matrix in order to give more flexible control of drug release, increasing the loading efficiency for drugs like PGE2 which possesses poor water solubility, and preventing drug leakage. Among the different approaches to modeling pulmonary fibrosis, bleomycin remains the most frequently used agent and can be given directly into the airway by intratracheal administration 20, 21 . The major advantage of the intratracheal bleomycin model is the short time between the drug instillation and the manifestation of fibrosis.…”

Orotracheal manganese‐enhanced MRI (MEMRI): An effective approach for lung tumor detection

“…Overall, these results support the growing interest in drug and contrast agent delivery via the airways to target and diagnose several diseases of the lungs, 18,53,54 but also of other organs. 49,55 The bulk of the literature seems to suggest that direct pulmonary administration is an effective, simple and reliable route for lung and systemic delivery of drugs. [56][57][58] Further studies are needed to shed light on this efficient and promising administration route.…”