SPIO processing in macrophages for MPI: The breast cancer MPI-SNLB-concept

Abstract

Abstract Introduction Breast cancer (BC) is the most common cancer in women worldwide. We aim to develop a new sentinel lymph node biopsy (SLNB) method with superparamagnetic iron oxide nanoparticles (SPIOs) and magnetic particle imaging (MPI) in BC to avoid tissue damaging while axillary surgery. As we know from i.v. SPIO application in magnetic resonance imaging (MRI), macrophages (MP) are key role player in processing of SPIOs (e.g. in liver) causing a drop of signal intensity. But, knowledge lacks concerning enrichment processes of SPIOs after injection in breast tissue, the adjacent lymphatic tissues and associated cells, especially in BC and metastatic lymph nodes. We already evaluated the distribution of SPIOs in an in vivo healthy and tumor mouse model. Based on these studies we investigate the processing of the SPIOs in MP. Material and Methods To evaluate SPIO processing, a mouse MP cell line J774A.1 was incubated either by Resovist in culture medium (RPMI, FBS), or culture medium only as control. MP were than analyzed by transmission electron microscopy (TEM). Additionally, this process was observed in vivo by multiphoton microscopy. Detection of SPIOs was realized by excitation at 1200 nm. Results Resovist had no toxic effects on cells.MP showed activity in phagocytosis of Resovist after incubation in TEM as well as in multiphoton microscopy. SPIOs were detectable within intracellular vesicles by TEM and 3-photon process. The first cell associated SPIO signal was detected after 1,5 min of incubation by in vivo imaging. Conclusion To our knowledge this is the first time a 3-photon device was used to image SPIOs in a bio-medical context. System wide scanning is known (MRI, MPI), but nowwe are also able to identify the link to subcellular processing and localization of SPIOs. Further processing of SPIOs in MP is under development.