Purpose: To investigate the usefulness of magnetic particle imaging (MPI) for predicting the therapeutic effect of magnetic hyperthermia (MH). Materials and Methods: First, we performed phantom experiments to investigate the relationship between the MPI value and the temperature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). The MPI value was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals. Samples filled with various iron concentrations of MNPs (Resovist ®) were prepared and were imaged using our MPI scanner. These samples were also heated using the AMF, and the specific loss power (SLP) and volume-specific loss power (vSLP) were calculated from the initial slope of the time-dependent temperature rise. Second, we performed animal experiments using tumor-bearing mice, which were divided into untreated (n = 10) and treated groups (n = 20). The tumors in the treated group were injected with Resovist ® at an iron concentration of 250 mM (n = 10) or 500 mM (n = 10), and received MH for 20 min, during which the temperatures in the tumor and rectum were measured. The relative tumor volume growth (RTVG) was calculated from (V 15 − V 0)/V 0 , where V 0 and V 15 represented the tumor volume on day 0 and day 15 after MH, respectively. Results: In phantom experiments, the MPI value had significant correlations with the iron concentration of MNPs (r = 0.997), temperature rise (r = 0.981), and vSLP (r = 0.961). In animal experiments, the MPI value had significant correlations with the temperature rise in the tumor (r = 0.731) and RTVG (r = −0.687). Conclusion: Our preliminary results suggest that MPI is useful for predicting the therapeutic effect of MH.

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.

Purpose: Magnetic hyperthermia treatment (MHT) is a strategy for cancer therapy using the temperature rise of magnetic nanoparticles (MNPs) under an alternating magnetic field (AMF). Recently, a new imaging method called magnetic particle imaging (MPI) has been introduced. MPI allows imaging of the spatial distribution of MNPs. The purpose of this study was to investigate the feasibility of visualizing and quantifying the intratumoral distribution and temporal change of MNPs and predicting the therapeutic effect of MHT using MPI. Materials and Methods: Colon-26 cells (1 × 10 6 cells) were implanted into the backs of eight-week-old male BALB/c mice. When the tumor volume reached approximately 100 mm 3 , mice were divided into untreated (n = 10) and treated groups (n = 27). The tumors in the treated group were directly injected with MNPs (Resovist ®) with iron concentrations of 500 mM (A, n = 9), 400 mM (B, n = 8), and 250 mM (C, n = 10), respectively, and MHT was performed using an AMF with a frequency of 600 kHz and a peak amplitude of 3.5 kA/m. The mice in the treated group were scanned using our MPI scanner immediately before, immediately after, 7 days, and 14 days after MHT. We drew a region of interest (ROI) on the tumor in the MPI image and calculated the average, maximum, and total MPI values and the number of pixels by taking the threshold value for extracting the contour as 40% of the maximum MPI value (pixel value) within the ROI. These parameters in the untreated group were taken as zero. We also measured the relative tumor volume growth (RTVG) defined by (V−V0)/V0, where V 0 and V are the tumor volumes immediately before and after MHT, respectively. Results:

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INTRODUCTION:Recently, 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. The application of this approach with use of nebulized MNPs to lung cancer has also been considered. The development of a method to specifically image MNPs is desired to realize this therapeutic strategy. This study was undertaken to investigate the feasibility of applying magnetic particle imaging (MPI) to pulmonary imaging using nebulized MNPs and to evaluate the usefulness and reliability of this approach using phantom and small animal experiments. METHODS:In phantom experiments, we prepared a Y-shaped bifurcated tube made of Teflon which simulated tracheal bifurcation, and connected an inhaler to the outlets of the tube. We then nebulized MNPs using a nebulizer and they were sucked from the inlet of the bifurcated tube to the outlets. Furthermore, we placed the urethane sponges simulating pulmonary tissues at the left and right outlets of the bifurcated tube. We also placed two flowmeters between the inhaler and Y-shaped bifurcated tube to control the flow of nebulized MNPs. In addition, we put a neodymium magnet (0.5 Tesla) on the bifurcation of the Y-shaped tube. After the experiment, we imaged the urethane sponges using our MPI scanner [1, 2] and calculated an asymmetry index (AI) from (L-R)/(L+R), where L and R represent the MPI values of the urethane sponge at the left and right outlets of the Y-shaped bifurcated tube, respectively. In this study, the MPI value was defined as the pixel value of the transverse image reconstructed from the third-harmonic signals extracted using a gradiometer coil and a lock-in amplifier [1, 2]. We then investigated the relationships between the AI value and the distance between the Y-shaped bifurcated tube and neodymium magnet and between the AI value and flow rate.In animal experiments, seven-week-old male ICR mice were used. Intrapulmonary administration of MNPs was performed using a nebulizing microsprayer connected to a high-pressure syringe containing 50 L of MNPs (Resovist ). We imaged the lungs using our MPI scanner [1, 2] two and a half hours after the intrapulmonary administration of MNPs. After the MPI studies, X-ray CT images were obtained using a 4-row multi-slice CT scanner. The MPI image was co-registered with the X-ray CT image using parameters for magnification and rotation that were previously obtained using a phantom with 3 point sources. RESULTS:In phantom experiments, there was an excellent negative correlation between the AI value and the distance between the bifurcated tube and neodymium magnet (r=-0.995). The AI value decreased significantly with increasing flow rate, and there was also a significant negative correction between the AI value and flow rate (r=-0.958). These results suggest that MPI is useful for monitoring the effect...