Abstract

Purpose: To investigate the feasibility of applying magnetic particle imaging (MPI) to pulmonary imaging using nebulized magnetic nanoparticles (MNPs) and to quantify the mucociliary clearance in the lung, using small animal experiments. Materials and Methods: Intrapulmonary administration of MNPs was performed in seven-week-old male ICR (Institute of Cancer Research) mice (n = 8) using a nebulized microsprayer connected to a high-pressure syringe containing 50 μL of MNPs (500 mM Resovist®). We imaged the lungs using our MPI scanner 2.5 hours, 1 day, 3 days, and 7 days after the intrapulmonary administration of MNPs. The average MPI value was calculated by drawing a region of interest (ROI) on the lungs by taking the threshold value for extracting the contour as 20% of the maximum MPI value within the ROI. The MPI value was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. Mice were sacrificed immediately after the last MPI and X-ray CT studies on day 7, and 5 lobes of the lung in each mouse were extracted to confirm the accumulation of iron using Berlin blue staining. Results: We could visualize the distribution of MNPs in the lungs as positive contrast using MPI with use of nebulized MNPs. The presence of iron in the lung was confirmed by Berlin blue staining. The average MPI value decreased with time and tended to saturate. The clearance rate was calculated to be 0.505 day−1 from the time course of the average MPI value in the lungs. Conclusion: Our preliminary results suggest that MPI can be applied to pulmonary imaging by nebulizing MNPs and can be useful for quantifying the mucociliary clearance in the lung.

Highlights

  • A magnetic targeting method has been proposed for localizing drug carriers such as liposomes containing both magnetic nanoparticles (MNPs) and drugs in the objective organ or tissue by applying an external magnetic field, and it attracts attention as a next-generation therapeutic strategy for cancer [1] [2]

  • We have developed a system for magnetic particle imaging (MPI) with a field-free-line encoding scheme, in which the field-free line is generated using two opposing neodymium magnets, and transverse images are reconstructed from the third-harmonic signals received by a gradiometer coil using the maximum likelihood-expectation maximization (ML-EM) algorithm [7] [8]

  • We investigated the feasibility of applying MPI to pulmonary imaging in mice using nebulized MNPs

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Summary

Introduction

A magnetic targeting method has been proposed for localizing drug carriers such as liposomes containing both magnetic nanoparticles (MNPs) and drugs in the objective organ or tissue by applying an external magnetic field, and it attracts attention as a next-generation therapeutic strategy for cancer [1] [2]. The application of this approach with use of nebulized MNPs to lung diseases has been considered [1]. The development of a method to and quantitatively monitor the mucociliary clearance of drug carriers is desired to enhance the usefulness of the aerosol-based approach of drug delivery

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