Tracking the fates of iron-labeled tumor cells in vivo using magnetic particle imaging.

The use of imaging to detect and monitor the movement and accumulation of cells in living subjects can provide significant insights that can improve our understanding of metastasis and guide therapeutic development. For cell tracking using Magnetic Resonance Imaging (MRI), cells are labeled with iron oxides and the effects of the iron on water provides contrast. However, due to low specificity and difficulties in quantification with MRI, other modalities and approaches need to be developed. Magnetic Particle Imaging (MPI) is an emerging imaging technique which directly detects iron, allowing for a specific, quantitative and sensitive readout. Here, we use MPI to image iron-labeled tumor cells longitudinally, from implantation and growth at a primary site to movement to distant anatomic sites. In vivo bioluminescent imaging (BLI) was used to localize tumor metastases and computed tomography (CT) allowed for correlation of these signals to anatomic locations. These three imaging modalities provide information on immune escape and metastasis of iron-labeled, and unlabeled, tumor cells, and the accumulation of cell-free iron contrast over time. We localized iron signals by MPI and tumor cells via BLI, and correlated these positive contrast images with CT scans to reveal the anatomic sites with cancer cells; histologic analysis confirmed the presence of iron-labeled tumor cells in the tissues, suggesting that the metastatic cells retained enough iron for MPI detection. The use of multi-modality cell tracking reveals the movement, accumulation and fates of labeled cells that will be helpful understanding cancer progression and guiding the development of targeted therapies.

Magnetic Particle Imaging of Magnetotactic Bacteria as Living Contrast Agents Is Improved by Altering Magnetosome Arrangement.

Superparamagnetic iron oxide nanoparticles (SPIONs) can be used as imaging agents to differentiate between normal and diseased tissue or track cell movement. Magnetic particle imaging (MPI) detects the magnetic properties of SPIONs, providing quantitative and sensitive image data. MPI performance depends on the size, structure, and composition of nanoparticles. Magnetotactic bacteria produce magnetosomes with properties similar to those of synthetic nanoparticles, and these can be modified by mutating biosynthetic genes. The use of Magnetospirillum gryphiswaldense, MSR-1 with a mamJ deletion, containing clustered magnetosomes instead of typical linear chains, resulted in improved MPI signal and resolution. Bioluminescent MSR-1 with the mamJ deletion were administered into tumor-bearing and healthy mice. In vivo bioluminescence imaging revealed the viability of MSR-1, and MPI detected signals in livers and tumors. The development of living contrast agents offers opportunities for imaging and therapy with multimodality imaging guiding development of these agents by tracking the location, viability, and resulting biological effects.

Magnetic Particle Imaging of Macrophages Associated with Cancer: Filling the Voids Left by Iron-Based Magnetic Resonance Imaging.

PURPOSE: Magnetic particle imaging (MPI) is an emerging molecular imaging technique that directly detects iron nanoparticles distributed in living subjects. Compared with imaging iron with magnetic resonance imaging (MRI), MPI signal can be measured to determine iron content in specific regions. In this paper, the detection of iron-labeled macrophages associated with cancer by MRI and MPI was compared. PROCEDURES: Imaging was performed on 4T1 tumor-bearing mice 16-21 days post-cancer cell implantation, 24 h after intravenous injection of Ferucarbotran, a superparamagnetic iron oxide (SPIO) or Ferumoxytol, an ultra-small SPIO. Images of living mice were acquired on a 3T clinical MRI (General Electric, n = 6) or MPI (Magnetic Insight, n = 10) system. After imaging, tumors and lungs were removed, imaged by MPI and examined by histology. RESULTS: MRI signal voids were observed within all tumors. In vivo, MPI signals were observed in the tumors of 4 of 5 mice after the administration of each contrast agent and in all excised tumors. Signal voids visualized by MRI were more apparent in tumors of mice injected with Ferumoxytol than those that received Ferucarbotran; this was consistent with iron content measured by MPI. Signal voids relating to macrophage uptake of iron were not detected in lungs by MRI, since air also appears hypointense. In vivo, MPI could not differentiate between iron in the lungs vs the high signal from iron in the liver. However, once the lungs were excised, MPI signal was detectable and quantifiable. Histologic examination confirmed iron within macrophages present in the tumors. CONCLUSIONS: MPI provides quantitative information on in vivo iron labeling of macrophages that is not attainable with MRI. The optimal iron nanoparticle for MPI in general is still under investigation; however, for MPI imaging of macrophages labeled in vivo by intravenous administration, Ferumoxytol nanoparticles were superior to Ferucarbotran.