Tracking short-term biodistribution and long-term clearance of SPIO tracers in magnetic particle imaging

Abstract

Magnetic particle imaging (MPI) is an emerging tracer-based medical imaging modality that images non-radioactive, kidney-safe superparamagnetic iron oxide (SPIO) tracers. MPI offers quantitative, high-contrast and high-SNR images, so MPI has exceptional promise for applications such as cell tracking, angiography, brain perfusion, cancer detection, traumatic brain injury and pulmonary imaging. In assessing MPI's utility for applications mentioned above, it is important to be able to assess tracer short-term biodistribution as well as long-term clearance from the body. Here, we describe the biodistribution and clearance for two commonly used tracers in MPI: Ferucarbotran (Meito Sangyo Co., Japan) and LS-oo8 (LodeSpin Labs, Seattle, WA). We successfully demonstrate that 3D MPI is able to quantitatively assess short-term biodistribution, as well as long-term tracking and clearance of these tracers in vivo.

Figure 1

Chemical diagrams of the tracer coatings.

Figure 2

Flowchart of the tracer biodistribution and long-term clearance animal experiment.

Figure 3

A series of dilutions were performed to demonstrate the linearity of MPI signal with particle concentration. On the left is a photograph of LS-008 point sources and the corresponding maximum projection intensity MPI image as well as the plot of MPI signal versus Fe concentration. On the right is a photograph of Ferucarbotran point sources and the corresponding maximum projection intensity MPI image as well as the plot of MPI signal versus Fe concentration. In both cases the MPI signal is linear with Fe concentration.

Figure 4

Short-term biodistribution of Ferucarbotran (top) and LS-008 (bottom) at 4 time points as seen in MPI (dose: 5 mg of Fe / kg for both tracers). The MPI images were overlaid onto projection X-ray images for anatomical reference. In both sets of images the tracer immediately begins to clear to the liver and spleen. For LS-008 tracer, in addition the liver and spleen, we can see what are probably the jugular veins as well as the lungs and heart of the animal. Unlike Ferucarbotran that was designed to immediately clear to the liver, LS-008 stays in circulation. The drastic difference in biodistribution for the two tracers is clearly captured by MPI.

Figure 5

Average MPI signal in the ROI over the jugular vein of a rats (n = 3) injected with Ferucarbotran, rats (n = 3) injected with LS-008 and rats (n = 3) not injected with anything showing short-term tracer clearance from blood. For rats injected with Ferucarbotran and control rats no discernible jugular vein could be seen in the image so a large box was drawn over the region where jugular vein was estimated to be from the corresponding X-Ray image. The interference noise is an average signal in an ROI drawn over a region outside the body. As expected, LS-008 stays in the blood (half-life 4.2 h ± 0.5 h), while Ferucarbotran is almost immediately cleared to the liver. There is no detectable signal from the control animals. The inset within the dashed line is the data collected during the 1st hour.

Figure 6

MPI images of rats injected with Ferucarbotran (top) and LS-008 (bottom) overlaid onto projection X-ray images for anatomical reference. Both tracers were injected at a dose of 5 mg of Fe / kg. MPI images show slow clearance of the tracer by the liver and spleen of a rat over a 70 day period. Ferucarbotran is predominantly cleared by the liver, while Ls-008 is predominantly cleared by the spleen.

Figure 7

(left) Long-term clearance of Ferucarbotran from the liver (half-life of 5.6 d ± 0.2 d) and the spleen (half-life of 4.0 d ± 0.5 d) of a group of rats (n=3). (right) Long-term clearance of LS-008 from the liver (half-life of 6.5 d ± 0.7 d) and the spleen (half-life of 18.2 d ± 2.5 d) or a group of rats (n=3). No signal above the interference noise floor was detected from the control animals.

Figure 8

Top panel shows a representative photograph of the ex vivo set-up with the Day 2 excised liver, spleen, kidneys, lungs and heart followed by MPI images of the Day 2 extracted organs for all animals injected with LS-008 and Ferucarbotran. The bottom panel is a similar photograph and MPI image of organs extracted at day 70 after the injection. At day 70, LS-008 signal is only observed in the spleen and Ferucarbotran signal is only observed in the liver.

Figure 9

Ex vivo Organ measurements for Ferucarbotran and LS-008 at day 2 and day 70. As with in vivo data, LS-008 is cleared predominately through the spleen, while Ferucarbotran is cleared through the liver. No signal was seen in the heart, lungs or kidneys. And no signal was detected in the organs of the control animals.