Hyperpolarized 13C-labelled anhydrides as DNP precursors of metabolic MRI agents

Sonia Colombo Serra, Magnus Karlsson, Giovanni Battista Giovenzana, Camilla Cavallotti, Fabio Tedoldi, Silvio Aime

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

The extraordinary enhancement of the nuclear magnetic resonance (NMR) signal that can be obtained by dynamic nuclear polarization (DNP) techniques is prompting new avenues of research based on the in vivo detection of metabolic abnormalities associated with the onset and progression of human diseases. 13C-labelled short-chain fatty acids appear to be interesting candidates for this novel class of metabolic-active contrast agents (MCAs), as they have been shown to report on metabolic differences between healthy and ischaemic tissues in mice. In spite of their promising biological efficacy, the formulations of short-chain fatty acids that fulfil the many technical constraints of the DNP procedure, as it is today, may limit their clinical potential. New solutions have been sought to circumvent technology-related challenges and facilitate clinical translation of these molecules. In particular, it has been shown that, by using symmetric anhydrides as chemical precursors for short-chain fatty acids, no glass-forming additives are needed in the DNP formulations. Furthermore, novel esterified trityl radicals and lipophilic gadolinium complexes allow easy removal of the polarization-promoting additives at the end of the DNP process. By applying the three concepts reported, we have succeeded in preparing aqueous formulations of short-chain fatty acids for pharmaceutical use that have favourable properties compared with those obtained from current procedures. The use of organic derivatives as chemical precursors of the MCA of interest appears to be a generally valid concept, not restricted to symmetric anhydrides of fatty acids, which can markedly improve the clinical potential of other 13C-labelled compounds. Copyright (C) 2012 John Wiley & Sons, Ltd.
Original languageEnglish
JournalContrast Media & Molecular Imaging
Volume7
Issue number5
Pages (from-to)469-477
ISSN1555-4309
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

  • RADIOLOGY,
  • DYNAMIC NUCLEAR-POLARIZATION
  • C-13 MAGNETIC-RESONANCE
  • IN-VIVO
  • HEART
  • ACID
  • NMR
  • dynamic nuclear polarization
  • symmetric anhydrides
  • short-chain fatty acids
  • esterified electron polarizing agent

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