Directly detecting in vivo metabolisms utilizing a quantum sensing technology

Peptides, which are composed of amino acids, are important biomolecules that participate in biological processes through metabolisms, modifications, and interactions with proteins. For the development of diagnostic and therapeutic technologies, there is a growing interest in obtaining in vivo dynamics of peptides, including metabolisms and localizations. Hyperpolarization is a state-of-the-art technology that markedly improves the detection sensitivity of nuclear magnetic resonance (NMR) and magnetic resonance imaging (MRI), and it is recognized as a class of quantum sensing technologies. Hyperpolarization has been expected to be employed as the next-generation highly sensitive molecular imaging to obtain in vivo dynamics of molecules. However, the hyperpolarized signal rapidly decays back to the thermally equilibrated state. The molecular structures influence the lifetime of the hyperpolarized signal, and, thus, the application of hyperpolarization technology utilizing peptides has been limited to small-sized amino acids or dipeptides.

This study experimentally and computationally examined molecular structures of peptides to affect the hyperpolarization lifetime, and successfully developed oligopeptide-type hyperpolarized MRI molecular probes for in vivo studies. The glutathione-type molecular probe, one of the oligopeptide-type molecular probes developed in this study, was hyperpolarized, and the detection sensitivity of NMR/MRI was improved by more than 100,000 times. By intravenously injecting the hyperpolarized glutathione-type molecular probe into the acute kidney injury mouse model, the altered in vivo distribution and metabolic conversions of the probes were directly monitored by NMR/MRI. Because oligopeptides, which are the scaffold for the developed molecular probes in this study, are biological molecules that originally exist in the body and are involved in various biological phenomena, the developed oligopeptide-type molecular probes are expected to be applied to a non-invasive diagnostic imaging method for metabolic reactions and diseases in the future.

Papers

Journal: Science Advances

Title: Directly monitoring the dynamic in vivo metabolisms of hyperpolarized ¹³C-oligopeptides

Authors: Yohei Kondo, Yutaro Saito, Tomohiro Seki, Yoichi Takakusagi, Norikazu Koyasu, Keita Saito, Jumpei Morimoto, Hiroshi Nonaka, Koichiro Miyanishi, Wataru Mizukami, Makoto Negoro, Abdelazim E. Elhelaly, Fuminori Hyodo, Masayuki Matsuo, Natarajan Raju, Rolf E. Swenson, Murali C. Krishna, Kazutoshi Yamamoto, Shinsuke Sando*

DOI: 10.1126/sciadv.adp2533