Nanoparticle retention enables non-invasive detection of metastases by magnetic particle imaging in murine breast cancer models

Early detection of metastatic disease improves cancer survival, yet existing modalities are limited in their detection capabilities. We propose that magnetic particle imaging (MPI), an emerging technology, can be used for early detection of primary tumors and metastases. MPI detects minute quantities of magnetic particles that act as "cold tracers" which accumulate in areas of high immune activity. <b>Methods:</b> Pegylated Synomag® nanoparticles were intravenously injected into mouse models of breast cancer bearing primary tumors and spontaneously developed lung metastases. After 72 h, mice were subjected to three-dimensional MPI followed by structural imaging for co-registration. Non-tumor bearing mice served as controls for background signal correction and toxicity analysis. Animals were then sacrificed to collect tumors and organs of interest for two-dimensional MPI scans before fixing them for histopathological evaluation by hematoxylin and Eosin (H&E), Prussian blue, and immunohistochemistry staining. To further substantiate our findings towards clinical translation, tumor phantoms with nanoparticles were evaluated in a newly-built human scale MPI. <b>Results:</b> Pegylated Synomag® nanoparticles showed a strong signal in both <i>in vitro</i> and <i>in vivo</i> models. Multiple macro and micro metastatic sites were identified by MPI and later confirmed by histology. <i>Ex vivo</i> quantitative analysis showed MPI can detect metastasis with high specificity and sensitivity, with positive correlations between tumor burden and macrophage population in the tumor microenvironment. Towards clinical translation, we also demonstrate nanoparticle detection in tumor phantoms using a human-scale MPI. <b>Conclusion:</b> MPI using Pegylated Synomag® nanoparticles can successfully detect primary tumors and micrometastases away from large organs of the reticuloendothelial system. Nanoparticles were found in the tumor microenvironment, associated with stromal and immune cells, especially macrophages. This provides evidence to use MPI for noninvasive detection of highly inflammatory tumors and metastasis, as well as exploring their potential for other inflammatory diseases.