Description: The most used class of MRI probes for cellular imaging is represented by iron oxide nanoparticles (IONPs). Even if they succeeded at both preclinical and clinical levels in many cases, the negative constrast they produce as T2 or T2* contrast agents may be a drawback, making an unambiguous detection of the labelled cells very challenging especially in organs with an intrinsically low MRI signal (e.g. lung, bones) or in the presence of haemorrhages. In addition, the contrast generated by IONP-labelled cells is linearly correlated to the cells number only at low iron concentrations.
A new emerging approach for cellular MRI is based on agents containing fluorine (
F, 100% natural abundance).
F-based MRI has gained huge attention in the last 20 years, owing to the possibility to obtain quantitative information in a diagnostic MR protocol because of the absence of background signal allows specific and selective detection of the administrated
F-containing probes in vivo. Moreover, the chemical shift of
F is spread out over a wide range, thus allowing the selective observation of different agents present in the same anatomical district. The
F-containing contrast agents studied so far are mostly nanosized.
Because of their high payload of
F atoms, perfluorocarbons (PFCs), under the form of nanoemulsions, are the most frequently used
F-MRI contrast agents for biological applications. Recent studies have demonstrated the potential of PFCs to label and image cells (mostly phagocytic) either in vitro or in vivo and have demonstratedthe the potential of cellular
F-MRI, especially for quantifying the number of labelled cells.
This research project is focused on the development of a labelling procedure based on Glucan Particles (GPs), a high potential biocompatible microcarriers in the molecular imaging field, loaded with perfluoro-crown-ether. Our data showed that the use of loaded GPs improved substantially the labelling efficiency of macrophages in
F-MRI cellular imaging experiments in vitro. Further studies are in due course with the main goal to demonstrate the performance of PFCs-loaded GPs for the visualization and the tracking of the macrophage recruitment in an animal model.
Selected papers: Menchise, V., Digilio, G., Gianolio, E., Catanzaro, V., Carrera, C., Aime, S. In Vivo Labeling of B16 Melanoma Tumor Xenograft with a Thiol-Reactive Gadolinium Based MRI Contrast Agent Molecular Pharmaceutics (2011) 1750-1756 DOI: 10.1021/mp2001044.
Catanzaro, C., Gringeri, C. V., Menchise, V., Padovan, S., Boffa, C., Dastrù, W., Chaabane, L., Digilio, G., Aime, S. A R2p/R1p ratiometric procedure to assess Matrix Metalloproteinase-2 activity by Magnetic Resonance Imaging. Angew. Chem. Int. (2013), 52, 3926–3930. (DOI: 10.1002/anie.201209286).
Figueiredo, S., Cutrin, J.C., Rizzitelli, S., De Luca, E., Moreira, J.N., Geraldes, C.F., Aime, S., Terreno, E. MRI tracking of macrophages labeled with glucan particles entrapping a water insoluble paramagnetic Gd-based agent. Mol Imaging Biol. 2013;15:307-15.
Rizzitelli, S., Giustetto, P., Cutrin, J.C., Delli Castelli, D., Boffa, C., Ruzza, M., Menchise, V., Molinari, F., Aime, S., Terreno, E. Sonosensitive theranostic liposomes for preclinical in vivo MRI-guided visualization of doxorubicin release stimulated by pulsed low intensity non-focused ultrasound J Control Release 2015 Jan; 202C: 21-30 | PMID: 25626083.
Chirizzi C., Menchise, V., Delli Castelli, D., Dastrù, W., Aime. S. and Terreno, E. Glucan Particles Loaded with Fluorinated Emulsions: a Sensitivity Improvement for the Visualization of Phagocytic Cells by 19F-MRI 2015 submitted to Current Molecular Imaging.
MRI Tracking of Macrophages Labeled with Glucan Particles Entrapping perfluorocarbons based nanoparticles