Highly Adaptable 15N-Molecular Tags for Development of Novel Hyperpolarized Molecular Imaging Probes

Loading...
Thumbnail Image

Date

2022

Advisors

Journal Title

Journal ISSN

Volume Title

Repository Usage Stats

31
views
53
downloads

Abstract

Hyperpolarized magnetic resonance spectroscopic imaging (HP-MRSI) enables non-invasive visualization of metabolism and physiological activities in real-time. Hyperpolarized agents developed to date are primarily 13C-labeled metabolites with short polarization lifetimes of less than a minute, limiting the imaging assay to fast metabolic pathways. To expand on the applications of HP-MRSI, we proposed the use of a versatile 15N-molecular tagging strategy.

This dissertation reports our exploration and application of highly adaptable 15N-molecular handles for development of hyperpolarized molecular imaging probes. Towards this goal, we have investigated 15N2-diazirines and 15N3-azides as biocompatible HP tags with long polarization lifetimes. Several 15N-tagged biological molecules were prepared, including amino acid, glucose, and drug molecules. Hyperpolarization with a d-DNP method demonstrated high signal enhancements (over 400,000-fold) and long 15N relaxation lifetimes (T1) of average 3–4 minutes in aqueous solutions, which warrants a long MR imaging window.

Moreover, we have rationally designed and synthesized novel 15N-labeled reaction-based probes for sensing hydrogen peroxide (H2O2) and nitric oxide (NO) as biomarkers for oxidative stress. We were able to observe the 15N-signal from our 15N-labeled H2O2 sensing probe in vivo using an animal model, which presents exciting progress in the field. Additionally, we explored various molecular probe designs to pursue the most practical 15N-labeled gamma-glutamyl transferase (GGT) sensor. These reaction-based redox and enzyme sensing probes showed favorable hyperpolarization and bioimaging properties. Our work on innovative de novo chemical probes highlights the unprecedented HP-MRSI applications for imaging disease biomarkers.

Department

Description

Provenance

Citation

Citation

Park, Hyejin (2022). Highly Adaptable 15N-Molecular Tags for Development of Novel Hyperpolarized Molecular Imaging Probes. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/25165.

Collections


Dukes student scholarship is made available to the public using a Creative Commons Attribution / Non-commercial / No derivative (CC-BY-NC-ND) license.