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内容記述 |
Peptides are involved in a variety of biological phenomena, such as metabolic control, immune response, and regulation of neural activity. Therefore, visualizing the metabolic dynamics of peptides, i.e., observing peptidase and protease activities within the body, is extremely significant for disease diagnosis and developing diagnostic and therapeutic methods.Nuclear magnetic resonance imaging (NMR/MRI) is a powerful technology that enables non-invasive detection of dynamic metabolisms in vivo. However, its inherently low sensitivity poses a significant challenge in detecting biomolecules at physiological concentrations. To overcome this limitation, we focused on dynamic nuclear polarization (DNP). DNP is a hyperpolarization technique that dramatically enhances NMR/MRI signal intensity.In this study, we report on the development of peptide-based DNP-MRI probes that can detect aminopeptidase (AP) activities in vivo. APs are enzymes that specifically cleave the N-terminal amino acid residue of peptides. We designed Ala-[1-13C]Gly-d2-NMe2 as an APN probe[1], and visualized its metabolism in tumor-bearing mice. For more advanced diagnostic approaches, we designed a series of DNP-MRI probes capable of simultaneous detection of multiple AP activities. Utilizing the developed probes, we succeeded in multiplexed analysis of AP activities within tumors. |
