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Abstract #3067

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

Kazutoshi Yamamoto1, Yohei Kondo2, Norikazu Koyasu1, Yutaro Saito3, Tomohiro Seki1, Yoichi Takakusagi4, Keita Saito4, Natarajan Raju5, Rolf E Swenson5, Shinsuke Sando3, and Murali C Krishna1
1National Cancer Institute, National Institutes of Health, Bethesda, MD, United States, 2School of Life Science and Technology, Institute of Science Tokyo, Yokohama, Kanagawa, Japan, 3Department of Chemistry and Biotechnology, The University of Tokyo, Bunkyo, Tokyo, Japan, 4National Institutes for Quantum Science and Technology, Inage, Chiba, Japan, 5National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD, United States

Synopsis

Keywords: Molecular Imaging, probes and targets, hyperpolarization

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.

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Keywords