Magnetic Particle Imaging Is a Sensitive In Vivo Imaging Modality for the Detection of Dendritic Cell Migration.

Abstract

The purpose of this study was to evaluate magnetic particle imaging (MPI) as a method for the in vivo tracking of dendritic cells (DC). DC are used in cancer immunotherapy and must migrate from the site of implantation to lymph nodes to be effective. The magnitude of the ensuing T cell response is proportional to the number of lymph node-migrated DC. With current protocols, less than 10% of DC are expected to reach target nodes. Therefore, imaging techniques for studying DC migration must be sensitive and quantitative. Here, we describe the first study using MPI to detect and track DC injected into the footpads of C57BL/6 mice migrating to the popliteal lymph nodes (pLNs). DC were labelled with Synomag-D™ and injected into each hind footpad of C57BL/6 mice (n = 6). In vivoMPI was conducted immediately and repeated 48h later. The MPI signal was measured from images and related to the signal from a known number of cells to calculate iron content. DC numbers were estimated by dividing iron content in the image by the iron per cell measured from a separate cell sample. The presence of SPIO-labeled DC in nodes was validated by ex vivo MPI, histology, and fluorescence microscopy. Day 2 imaging showed a decrease in MPI signal in the footpads and an increase in signal at the pLNs, indicating DC migration. MPI signal was detected in the left pLN in four of the six miceand two of the six mice showed MPI signal in the right pLN. Ex vivo imaging detected signal in 11/12 nodes. We report a sensitivity of approximately 4000 cells (0.015µg Fe) in vivo and 2000 cells (0.007µg Fe) ex vivo. Here, we describe the first study to use MPI to detect and track DC in a migration model with immunotherapeutic applications. We also bring attention to the issue of resolving unequal signals within close proximity, a challenge for any pre-clinical study using a highly concentrated tracer bolus that shadows nearby lower signals.