In vivo detection and imaging of aminopeptidase activities related to renin-angiotensin system using newly designed hyperpolarized MR probes

Motivation: Detection of aminopeptidase (AP) activities related to renin-angiotensin system (RAS) can lead to diagnosis of various diseases. Magnetic resonance imaging utilizing suitable hyperpolarized molecular probes can non-invasively detect in vivo AP activities. However, there have been no hyperpolarized molecular probes for APA, APB, and leucine AP. Goal(s): We aimed to design and develop new hyperpolarized molecular probes for the detection and imaging of RAS related AP activities in vivo. Approach: Based on the previously reported APN probe scaffold, three new hyperpolarized probes were designed. Results: Using the developed probes, target AP activities were successfully detected and visualized in vivo. Impact: This study exhibits a framework that artificially designed hyperpolarized molecular probes can detect in vivo aminopeptidase activities, which is assumed impossible with isotope labeled natural substrates and broadens the possibility of hyperpolarized MR diagnosis based on AP activities.