Directly Monitoring the Dynamic In Vivo Metabolisms of Hyperpolarized 13C Glutathione with Higher M.W. by Breaking Intrinsic 13C T1 Boundaries

Motivation: The emerging hyperpolarized MRI has been intrinsically limited for molecules with smaller molecular weights(M.W.~200) due to the limitation related to the long-standing bottleneck in their shorter lifetimes. Therefore, clinically promising peptide-based hyperpolarized probes with larger molecular weights have not been possible. Goal(s): We demonstrate our rationally designed structural-framework enables us to directly observe in vivo metabolic activities of a tripeptide, glutathione(M.W.300~), which plays a central role in cellular metabolisms. Approach: Designing hyperpolarized 13C-probes rationally and monitoring treatment responses on tumor xenografts were conducted. Results: The novel hyperpolarized 13C-GSH can successfully detect site-specific enzymatic activities in vivo and monitor treatment responses on tumor xenografts. Impact: This principal framework will pave the way for the future development of hyperpolarized probes, tumor characterizations, and advanced molecular imaging on clinically significant metabolic activities further, which can possibly lead to better prognostics, and earlier response monitoring in cancer treatment.