Development of cellular imaging procedures
Tracking cells in vivo by using imaging approaches represents a reliable method to assess the characteristics of cell grafts and to monitor their fate after transplantation. In that respect, minimally invasive techniques with high spatial resolution are desirable with a view of implementing therapeutic protocols in the clinical ordinary. MRI is a leading imaging modality enabling the non-invasive visualization of cell populations and their movements after transplantation in living animals with superb resolution. In order to be detectable, cells require to be adequately labelled with MRI contrast agents (CAs). Due to their excellent imaging efficiency, the superparamagnetic iron oxide nanoparticles (SPIONs) are regarded as the gold standard in cell-labeling. However, some issues are associated with their contrast generation mechanism based on signal-loss (negative contrast). As a promising alternative, paramagnetic CAs based on the metal Gadolinium (Gd) create a contrast increment (positive contrast) in T1-weighted (T1w) images, overcoming several complications related to the use of SPIONs. Even if toxic in the form of free aqueous ion, Gadolinium is generally considered safe when administered as a macrocyclic chelate and several agents have been approved for the clinical use so far. Differently from magnetic nanoparticles, large amounts of paramagnetic small molecules have to be delivered to target sites in order to be detected, and several labeling procedures have been developed to achieve this goal. In addition to Gd(III)-complexes, also fluorinated nanoparticles represent a valuable option for cellular imaging, especially for the visualization of the macrophage recruitment in inflammation sites or to tracking dendritic cells. One of the advantages of 19F-MRI is the possibility to quantify the signal and calculate the cellular content in the site of interest. Besides MRI, other imaging modalities can be used for tracking cells in vivo, like optical or photoacoustic imaging.