In vivo tracking and quantification of inhaled aerosol using magnetic particle imaging towards inhaled therapeutic monitoring

Pulmonary delivery of therapeutics is attractive due to rapid absorption and non-invasiveness but it is challenging to monitor and quantify the delivered aerosol or powder. Currently, single-photon emission computed tomography (SPECT) is used but requires inhalation of radioactive labels that typically have to be synthesized and attached by hot chemistry techniques just prior to every scan. Methods: In this work, we demonstrate that superparamagnetic iron oxide nanoparticles (SPIONs) can be used to label and track aerosols in vivo with high sensitivity using an emerging medical imaging technique known as magnetic particle imaging (MPI). We perform proof-of-concept experiments with SPIONs for various lung applications such as evaluation of efficiency and uniformity of aerosol delivery, tracking of the initial aerosolized therapeutic deposition in vivo, and finally, sensitive visualization of the entire mucociliary clearance pathway from the lung up to the epiglottis and down the gastrointestinal tract to be excreted. Results: Imaging of SPIONs in the lung has previously been limited by difficulty of lung imaging with magnetic resonance imaging (MRI). In our results, MPI enabled SPION lung imaging with high sensitivity, and a key implication is the potential combination with magnetic actuation or hyperthermia for MPI-guided therapy in the lung with SPIONs. Conclusion: This work shows how magnetic particle imaging can be enabling for new imaging and therapeutic applications of SPIONs in the lung.