Monitoring Glycolysis by Endogenous ³¹P CEST Magnetic Resonance Imaging.

Area of Science:

• Biochemistry
• Metabolic Engineering
• Medical Imaging

Background:

• Glycolysis is a fundamental metabolic pathway crucial for cellular energy production.
• Detecting low-concentration phosphate-containing metabolites in glycolysis is challenging with conventional methods.
• Phosphorus-31 Chemical Exchange Saturation Transfer (31P CEST) offers potential for sensitive metabolite detection.

Purpose of the Study:

• To develop and validate a novel 31P CEST approach for investigating glycolysis.
• To enable detection of endogenous phosphate-containing substrates below conventional detection limits.
• To assess metabolic differences in cancer cells and tissues using this technique.

Main Methods:

• Application of 31P CEST to monitor saturation transfer on inorganic phosphate (Pi) and phosphocreatine (PCr) signals.
• Selective irradiation of phosphate groups in endogenous molecules exchanging with ATP, Pi, and PCr.
• In vitro validation using mouse breast adenocarcinoma cell pellets (TS/A) with varying temperatures and glycolysis inhibition.
• In vivo experiments on murine mammary adenocarcinoma models.

Main Results:

• The 31P CEST method successfully amplified signals from low-concentration phosphate metabolites.
• In vitro studies confirmed the technique's sensitivity and specificity, correlating with glycolysis inhibition and temperature.
• 31P Z-spectra differentiated murine breast cancer cell lines with varying aggressiveness.
• In vivo 31P CEST distinguished between tumor and healthy tissues based on metabolic profiles.

Conclusions:

• 31P CEST is a powerful, non-invasive technique for assessing glycolysis and metabolic states.
• The method allows for sensitive detection of key phosphate metabolites, aiding in cancer research.
• This approach holds promise for differentiating tumor types and monitoring therapeutic responses.