In the field of Molecular Imaging, MRI stands out among the other modalities for the superb anatomical resolution, the high in-depth penetration and the possibility to exploit different mechanisms to generate contrast. The MRI contrast agents of common use (CAs) perturb the relaxation times of water protons and therefore do not allow displaying more than one event/molecule in the image because their effect on the water signal is not specific. It has been shown that multilabeling can be pursued by using frequency encoding CAs that include: 1) Chemical Exchange Saturation Transfer (CEST) agents; 2) hyperpolarized molecules; 3) heteronuclei-containing probes (e.g. 19F). CEST agents offer the considerable advantage of being able to be utilized in traditional 1H-MR experiments. The contrast is generated at will by simply applying a suitable RF pulse to selectively irradiate the NMR resonances of the exchangeable protons of the CA to be visualized. This unique property allows new applications such as the detection of more than one agent in the same MR image as well as the set-up of ratiometric methods for the quantitative evaluation of the physico-chemical and biological parameters that characterize the micro-environment in which the CAs are distributed. Different type of CEST CAs have been developed starting from paraCEST agents to arrive to lipoCEST and cellCEST probes. In particular, the macrocyclic complex YbHPDO3A can be used as pH reporter, providing high resolution maps of pH distribution inside tumors. In addition, DyHPDO3A-loaded erythrocytes act as reporters of the microvasculature. Finally, the analysis of the distribution of both these probes can be used to gain insights into the vascular permeability. These data allow us to obtain multiparametric maps of tumor, a tool of considerable importance for the characterization of the cancer microenvironment.

From paraCEST to lipo- and cellCEST: Routes to multiplex MRI detection

247th National Meeting (2014)

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