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

Abstract

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.

Thermo-Sensitive Nanomaterials: Recent Advance in Synthesis and Biomedical Applications

“…Moreover, nanomaterials can be used for not only imaging the physical location of cells, but also providing information on the biological state of cells [ 104 ]. Many types of NPs are under investigation as potential contrast agents for in vivo imaging such as MNPs, for instance, SPIONs [ 105 , 106 ] and AuNPs. In a recent publication, Zhou and collaborators have demonstrated the use of acetylated polyethylenimine (PEI)-entrapped AuNPs (Ac-PE-AuNPs) for precise diagnosis of hepatic carcinoma using negative computed tomography imaging [ 107 ].…”

Take a Deep Breath - Monitoring of Inhaled Nanoparticles with Magnetic Particle Imaging

“…Taken together with recent results from Zhou et al 22 , demonstrating the possibility of lung perfusion imaging with MPI, the authors completed the proof of concept of an MPI-based perfusion-ventilation mapping 21 . Perfusion-ventilation mapping is widely used in clinical routine for the diagnosis of pulmonary embolism and the preoperative evaluation of the lungs.…”

“…In this issue of Theranostics an excellent article titled “In Vivo Tracking and Quantification of Inhaled Aerosol using Magnetic Particle Imaging towards Inhaled Therapeutic Monitoring” was published by Tay et al 21 . In a well-designed and innovative study the authors showed that inhaled nanoparticles can be visualized by MPI in mice with accuracy comparable to radiolabeled aerosols.…”

Superparamagnetic iron oxides as MPI tracers: A primer and review of early applications

“…In this scenario, MPI has a real advantage, as SPIO detection is possible in all tissues with an equal sensitivity, as exemplified for the lung in Figure 4. This enables new MPI applications for the lung, including the study of (impaired) lung perfusion [51], or inhalation of aerosolized SPIO formulations [52], which was suggested to possibly serve as an alternative mucociliary clearance test. While 19 F MRI avoids the problems encountered with 1 H MRI and has been successfully used for lung ventilation imaging using fluorous gases, it suffers in from low sensitivity [53].…”