Nuclear hyperpolarization has emerged as a method to dramatically enhance the sensitivity of NMR spectroscopy. By application of this powerful tool, small molecules with stable isotopes have been used for highly sensitive biomedical molecular imaging. The recent development of molecular probes for hyperpolarized in vivo analysis has demonstrated the ability of this technique to provide unique metabolic and physiological information. This review presents a brief introduction of hyperpolarization technology, approaches to the rational design of molecular probes for hyperpolarized analysis, and examples of molecules that have met with success in vitro or in vivo.
Dynamic nuclear polarization (DNP) is a cutting-edge technique that markedly enhances the detection sensitivity of molecules using nuclear magnetic resonance (NMR)/magnetic resonance imaging (MRI). This methodology enables real-time imaging of dynamic metabolic status in vivo using MRI. To expand the targetable metabolic reactions, there is a demand for developing exogenous, i.e., artificially designed, DNP-NMR molecular probes; however, complying with the requirements of practical DNP-NMR molecular probes is challenging because of the lack of established design guidelines. Here, we report Ala-[1-
13
C]Gly-
d
2
-NMe
2
as a DNP-NMR molecular probe for in vivo detection of aminopeptidase N activity. We developed this probe rationally through precise structural investigation, calculation, biochemical assessment, and advanced molecular design to achieve rapid and detectable responses to enzyme activity in vivo. With the fabricated probe, we successfully detected enzymatic activity in vivo. This report presents a comprehensive approach for the development of artificially derived, practical DNP-NMR molecular probes through structure-guided molecular design.
Die Hyperpolarisation von Atomkernen bietet einen Weg, die NMR‐Empfindlichkeit erheblich zu steigern. Durch Anwendung dieses leistungsstarken Hilfsmittels wurden niedermolekulare Verbindungen mit stabilen Isotopen für die hochempfindliche biomedizinische Bildgebung genutzt. Die jüngste Entwicklung molekularer Sonden für die hyperpolarisierte In‐vivo‐Analyse hat gezeigt, dass diese Technik in der Lage ist, einzigartige metabolische und physiologische Informationen zu liefern. Dieser Aufsatz bietet eine kurze Einführung in die Technik der Hyperpolarisation, Ansätze zum rationalen Design molekularer Sonden für die hyperpolarisierte NMR‐Bildgebung und Beispiele von Molekülen, die erfolgreich in vitro oder in vivo für diesen Zweck genutzt wurden.
Molecular imaging can personalize cancer therapies by monitoring treatment responses, where hyperpolarized MRI is becoming an increasingly critical methodology. However, the limited number of available probes, which can interrogate key physiology/biochemistry related to targeted diseases, remains one of the major challenges in this growing field. In this presentation, we successfully demonstrate, for the first time, the advantages of newly synthesized 13C-Glutathione and 13C-N-acetyl cysteine probe in vivo redox status in a complementary manner. This approach serves as powerful non-invasive biomarkers to assess oxidative stress, which plays a vital role in various diseases and can be translatable to the clinical diagnosis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.