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 (19F, 100% natural abundance). 19F-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 19F-containing probes in vivo. Moreover, the chemical shift of 19F is spread out over a wide range, thus allowing the selective observation of different agents present in the same anatomical district. The 19F-containing contrast agents studied so far are mostly nanosized.
Because of their high payload of 19F atoms, perfluorocarbons (PFCs), under the form of nanoemulsions, are the most frequently used 19F-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 19F-MRI, especially for quantifying the number of labelled cells.
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.