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: 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:

When magnetic nanoparticles (MNPs) are used as a contrast agent for magnetic particle imaging (MPI), they are rapidly excreted during systemic circulation by the reticuloendothelial system such as Kupffer cells in the liver. Therefore, when considering clinical applications of MPI such as long-term monitoring of cardiovascular diseases, increasing the blood circulation time of MNPs by encapsulating the MNPs into actual cells such as red blood cells (RBCs) as a carrier may be practical. The purpose of this study was to create a biocompatible tracer for MPI by encapsulating MNPs (Resovist ®) into RBCs, and to investigate the effect of the encapsulating procedure on the properties of the RBCs loaded with MNPs (L-RBCs). MNPs were encapsulated into RBCs by the hypotonic dialysis method using a hypotonic buffer solution at three different osmotic pressures. Transmission (TEM) and scanning electron microscopic (SEM) images of the L-RBCs were obtained, and the saturation magnetic moment (Ms) was measured using vibrating sample magnetometry (VSM). From the response to a permanent magnet, the findings on TEM images, and the Ms values measured by VSM, we confirmed that RBCs were successfully loaded with MNPs using the hypotonic dialysis method. When the osmotic pressure was 80 mOsm, MNPs were not retained sufficiently inside the RBCs but were adhered to the membrane surface (TEM images), and RBCs lost their biconcave disc shape and shrunk after resealing (SEM images). At 160 mOsm, the Ms value was much lower than those at 80 and 120 mOsm. At 120 mOsm, the shape of RBCs was preserved (SEM images) and the Ms value was the highest when 0.2 ml (5.6 mg of Fe) of Resovist ® was added to the dialysis tube for loading. In conclusion, we successfully encapsulated MNPs into RBCs using the hypotonic dialysis method. Our results suggest that an osmotic pressure of 120 mOsm is optimal for encapsulating MNPs into RBCs using the hypotonic dialysis method.

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