Access Type

Open Access Thesis

Date of Award

January 2025

Degree Type

Thesis

Degree Name

M.S.

Department

Chemistry

First Advisor

Eduard Chekmenev

Abstract

Recent advances in hyperpolarization, particularly Signal Amplification by Reversible Exchange (SABRE), have enhanced molecular magnetic resonance imaging (MRI) for in vivo applications. This study investigates [15N3]metronidazole, a tri-nitrogen-labeled derivative of an FDA-approved antibiotic, as a hypoxia-sensitive imaging agent. Under hypoxic conditions, the nitroimidazole group undergoes stepwise reduction to an amino group, inducing significant 15N chemical shift changes (30–600 ppm). We aim to develop an iridium catalyst-free, biocompatible hyperpolarized (HP) [15N3]metronidazole formulation exhibiting robust polarization (up to 15%) and extended T1 lifetimes (~10 min). Three specific objectives guide this work: (1) formulation of a HP injectable with enhanced 15N detection, (2) evaluation of in vitro cytotoxicity, and (3) assessment of in vivo imaging performance. Although prior studies used dissolution DNP and SABRE-SHEATH techniques, none produced a biocompatible formulation. This approach offers a non-radioactive, non-ionizing MRI platform for hypoxia detection and may extend to other physiologically relevant 15N labeled compounds.

Included in

Chemistry Commons

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