Synthesis of 13C– Labeled Imaging Probes for Metabolic MRI Studies Using Hyperpolarization

Authors

• DS Sail
• ACL Opina
• S Matsumoto
• S Kishimoto
• O Vasalatiy
• JL Meier
• AH Kesarwala
• JB Mitchell
• MC Krishna
• RE Swenson

Abstract

One of the major obstacles in cancer biology is the monitoring and understanding of cancer metabolism in vivo because of the complexity of biochemical pathways and low concentration of crucial metabolites, rendering traditional MR imaging challenging due to its limited sensitivity. Dramatic improvements, however, have been demonstrated by an MR technique called hyperpolarization, by aligning the nuclear spins in one spin state in a magnetic field enhancing the signals of the reporter molecules by 10,000 – 100,000-fold. It uses standard MRI instruments with a hyperpolarizer capable of bringing a compound from 4 K to body temperature in seconds. The technique also requires synthesized molecules that are labeled with carbon-13 and deuterium at strategic sites to track the metabolism of normal and diseased tissues. Chemical tracers that are natural components of metabolic pathways can be injected in vivo where they are easily metabolized. The biochemical pathways can be followed through hyperpolarization so the difference in the metabolism between diseased and normal tissues can be visualized in real time. We have synthesized derivatives of succinate and ketoglutarate to detect mutations in cancer cells. In normal cell, isocitrate is metabolized to ketoglutarate by isocitrate dehydrogenase (IDH1). However, mutation in IDH1 impairs the tricarboxylic acid (TCA) cycle where α-ketoglutarate is reduced to 2-hydroxyglutarate. Hence, these hyperpolarized probes demonstrate a strong potential to serve as real- time metabolic imaging probes for cancer studies.

Scientific Focus Area: Research Support Services

This page was last updated on Friday, March 26, 2021