A Magnetic Resonance Imaging‐Chemical Exchange Saturation Transfer (MRI‐CEST) Method for the Detection of Water Cycling across Cellular Membranes

Author:

Di Gregorio Enza1ORCID,Papi Chiara1ORCID,Conti Laura1ORCID,Di Lorenzo Antonino1ORCID,Cavallari Eleonora1ORCID,Salvatore Marco2ORCID,Cavaliere Carlo2ORCID,Ferrauto Giuseppe1ORCID,Aime Silvio2ORCID

Affiliation:

1. Department of Molecular Biotechnologies and Health Sciences University of Torino Via Nizza 52 10126 Torino Italy

2. IRCCS SDN SynLab Via E. Gianturco 113 80143 Napoli Italy

Abstract

AbstractWater cycling across the membrane transporters is considered a hallmark of cellular metabolism and it could be of high diagnostic relevance in the characterization of tumors and other diseases. The method relies on the response of intracellular proton exchanging molecules to the presence of extracellular Gd‐based contrast agents (GBCAs). Paramagnetic GBCAs enhances the relaxation rate of water molecules in the extracellular compartment and, through membrane exchange, the relaxation enhancement is transferred to intracellular molecules. The effect is detected at the MRI‐CEST (Magnetic Resonance Imaging ‐ Chemical Exchange Saturation Transfer) signal of intracellular proton exchanging molecules. The magnitude of the change in the CEST response reports on water cycling across the membrane. The method has been tested on Red Blood Cells and on orthotopic murine models of breast cancer with different degree of malignancy (4T1, TS/A and 168FARN). The distribution of voxels reporting on membrane permeability fits well with the cells’ aggressiveness and acts as an early reporter to monitor therapeutic treatments.

Funder

European Commission

Ministero dell’Istruzione, dell’Università e della Ricerca

Ministero dell'Università e della Ricerca

Publisher

Wiley

Subject

General Chemistry,Catalysis

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