Abstract

The advent of nuclear spins hyperpolarization techniques represents a breakthrough in the field of medical diagnoses by magnetic resonance imaging. Dynamic nuclear polarization (DNP) is the most widely used method, and hyperpolarized metabolites such as [1-(13)C]-pyruvate are shown to report on status of tumours. Parahydrogen-induced polarization (PHIP) is a chemistry-based technique, easier to handle and much less expensive in respect to DNP, with significantly shorter polarization times. Its main limitation is the availability of unsaturated precursors for the target substrates; for instance, acetate and pyruvate cannot be obtained by direct incorporation of the parahydrogen molecule. Herein we report a method that allows us to achieve hyperpolarization in this kind of molecule by means of a tailored precursor containing a hydrogenable functionality that, after polarization transfer to the target (13)C moiety, is cleaved to obtain the metabolite of interest. The reported procedure can be extended to a number of other biologically relevant substrates.

Highlights

  • The advent of nuclear spins hyperpolarization techniques represents a breakthrough in the field of medical diagnoses by magnetic resonance imaging

  • Recent years have witnessed a renewed interest in routes to hyperpolarization as a means of overcoming sensitivity issues associated with magnetic resonance spectroscopy and magnetic resonance imaging (MRI)

  • Most attention has been devoted to the application of the dissolution Dynamic nuclear polarization (DNP) methodologies[1,2,3]

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Summary

Introduction

The advent of nuclear spins hyperpolarization techniques represents a breakthrough in the field of medical diagnoses by magnetic resonance imaging. Recent years have witnessed a renewed interest in routes to hyperpolarization as a means of overcoming sensitivity issues associated with magnetic resonance spectroscopy and magnetic resonance imaging (MRI) In this context, most attention has been devoted to the application of the dissolution DNP (dynamic nuclear polarization) methodologies[1,2,3]. An attempt to tackle the major limitations of PHIP has been pursued with the recently introduced signal amplification by reversible exchange method[21,22,23] With this approach, parahydrogen protons are not added to the substrate but the hyperpolarization transfer takes place on a transient adduct formed by the substrate, parahydrogen and the organometallic complex. Optimal polarization transfer has been observed when the added parahydrogen protons are two and three bonds away from the ‘target’ heteronucleus (Fig. 1, structure a)

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