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

Radioactively labeled deoxyglucose and choline are the leading molecular imaging probes for positron emission tomography (PET). The clinical applications for this imaging modality include brain function, cardiac imaging, and inflammation, along with oncological applications which are taking the lead. The radiation exposure associated with these examinations is limiting the use of this powerful technology in repeated examinations, in specific populations (pregnant women and children), as a screening tool for the wide population, and as a clinical research tool.Hyperpolarized magnetic resonance imaging (MRI) is an evolving pre-clinical and clinical imaging modality which is non-invasive and non-radioactive. As in PET, the molecular imaging probe used is at the heart of this examination. Originally developed for the purpose of distinguishing the metabolic products of the injected molecular probe, our group, in collaborations with researchers abroad, is a pioneer in showing that direct imaging of specific molecular probes (stable isotope labeled choline and glucose analogs) with hyperpolarized MRI is capable of showing specific tissue uptake, a pre-requisite for diagnostic imaging.The purpose of the current proposal is to establish hyperpolarized MRI capabilities in our own lab and reach two general goals: 1) to use various physiological and pharmacological models to further establish and characterize the conditions in which non-radioactive choline and glucose analogs and derivatives can be useful as imaging probes; and 2) to investigate further the molecular probe that is best suitable for these imaging applications in terms of pharmacokinetics, metabolism, and imaging efficiency. Our focus will be on 1) the actual chemical entity of the probes - where citicoline and deoxyglucose are promising candidates; and 2) the stable isotope labeling strategy. The overriding goal is to aid in translation of this pre-clinical imaging approach to clinical use.