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Citicoline and deoxyglucose as new molecular imaging probes of DNP hyperpolarized MRI for cancer and neuroimaging

Final Report Summary - HYPERPOLARIZED MRI (Citicoline and deoxyglucose as new molecular imaging probes of DNP hyperpolarized MRI for cancer and neuroimaging)

This ERC project focused on finding molecular imaging probes for a new type of medical imaging modality named hyperpolarized MRI. This technique enables the radiologist to obtain MRI images that are non-invasive and non-radioactive using contrast agents or molecular imaging probes that are based on metabolites and materials that do not pose a risk to the subject and leave no traces behind. The research originally focused on two such compounds – deoxyglucose and citicoline. Deoxyglucose underwent specialized synthesis to introduce stable-isotopes to the molecule and was found to be a very promising molecular imaging probe. Citicoline was found to be a no-go target. Several ex vivo systems were developed for the research on the deoxyglucose analog as well as on other hyperpolarized metabolic precursors that may be used as molecular imaging probes. Several other novel molecular imaging probes were identified and researched such as inorganic phosphate (that could report on extracellular pH changes and ischemic conditions), 15N-labelled urea and nitrate (that could report on blood flow and retention of the blood in tissue- which may highlight malignant lesions). The new ex vivo systems allowed investigation of pyruvate metabolism in real-time in the brain, liver, and tumors (hepatoma and breast cancer). Real-time metabolic monitoring in these systems (within a time frame of 30-60 seconds) showed multiple ways in which pyruvate metabolism could indicate human diseases and conditions such as stroke, cardiac ischemia, liver malignancy, and breast cancer.