Abstract #3182

Development of a DNP-MRI molecular probe for detecting dipeptidyl peptidase-4 activity in vivo based on the substrate recognition mechanism.

Akihito Goto¹, Hiroyuki Yatabe¹, Norikazu Koyasu², Kazutoshi Yamamoto², Mural Cherukuri Krishna², Keita Saito³, Yoichi Takakusagi³, Yutaro Saito¹, and Shinsuke Sando¹

¹The University of Tokyo, Tokyo, Japan, ²National Institutes of Health, Bethesda, MD, United States, ³National Institutes of Quantum Science and Technology, Chiba, Japan

Synopsis

Keywords: Molecular Imaging, Hyperpolarized MR (Non-Gas), DNP-MRI molecular probe, DPP-4

Motivation: Dipeptidyl peptidase-4 (DPP-4) is a biologically important peptidase known as a biomarker and therapeutic target for type 2 diabetes and cancers. Therefore, detection of DPP-4 activity can be a useful method for early diagnosis and treatment efficacy assessment.

Goal(s): Development of a DNP-MRI molecular probe for detecting DPP-4 activity in vivo

Approach: We performed molecular designs of DNP-MRI molecular probes for meeting physicochemical properties. For evaluation of enzymatic reactivity of the probes, enzymatic reaction parameters (K_m, k_cat) were measured. The optimized probe was applied for DNP-MRI experiments using mice.

Results: We developed a DNP-MRI molecular probe to detect DPP-4 activity in vivo.

Impact: With design strategy based on recognition mechanism, we have developed a DNP-MRI molecular probe against DPP-4, which has been difficult to develop so far. New probe enables detection of DPP-4 activity in vivo and will be useful for medical applications.

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