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

This study aims at determining lung distribution of gadolinium-based polysiloxane nanoparticles, AGuIX First, the aerodynamic size distribution and the aerosol output rate were thoroughly characterized. Then, a multimodal approach using magnetic resonance (MR) and gamma-camera (GC) imaging allows to assess the deposition of the aerosolised nanoparticles in the respiratory tract using isolated ventilated porcine lungs. The SRP has proven to be radiolabelled by radioisotope with a good yield. Crude SRP or radiolabelled ones showed the same aerodynamic size distribution and output as a conventional molecular tracer, as sodium fluoride. With MR and GC imaging approaches, the nebulised dose represented about 50% of the initial dose of nanoparticles placed in the nebuliser. Results expressed as proportions of the deposited aerosol showed approximately a regional aerosol deposition of 50% of the deposited dose in the lungs and 50% in the upper airways. Each technique assessed a homogeneous pattern of deposited nanoparticles in Lungs. MR observed a strong signal enhancement with the SRP, similar to the one obtained with a commonly used MRI contrast agent, gadoterate meglumine. As a known theranostic approach by intravenous administration, SRP appeared to be easily aerosolised with a conventional nebuliser. The present work proves that pulmonary administration of SRP is feasible in a human-like model and allows multimodal imaging with MR and GC imaging. This work presents the proof of concept of SRP nebulisation and aims to generate preclinical data for the potential clinical transfer of SRP for pulmonary delivery.

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© 2020 Montigaud et al.

Déclaration de conflit d'intérêts

FL and OT must disclose the patent WO2011/135101. FL, OT and YC must disclose the patent WO2013153197. These patents protect the AGuIX® nanoparticles described in this publication and their administration via the airways. FL, OT and YC are employees from NH TherAGuIX® that is developing the AGuIX® Nanoparticles. FL and OT possess shares of this company. OT reports grants, personal fees from NH TherAguix, during the conduct of the study; In addition, OT has a patent WO200550302 licensed. FL reports grants, personal fees from Nh TherAguix, during the conduct of the study and outside the submitted work. YC reports personal fees from NH TherAguix, outside the submitted work. The aforementioned authors report no other potential conflicts of interest in this work. The other authors report no conflicts of interest in this work.