Real-Time Interrogation of Aspirin Reactivity, Biochemistry, and Biodistribution by Hyperpolarized Magnetic Resonance Spectroscopy

Angew Chem Int Ed Engl. 2019 Mar 22;58(13):4179-4183. doi: 10.1002/anie.201812759. Epub 2019 Feb 20.

Abstract

Hyperpolarized magnetic resonance spectroscopy enables quantitative, non-radioactive, real-time measurement of imaging probe biodistribution and metabolism in vivo. Here, we investigate and report on the development and characterization of hyperpolarized acetylsalicylic acid (aspirin) and its use as a nuclear magnetic resonance (NMR) probe. Aspirin derivatives were synthesized with single- and double-13 C labels and hyperpolarized by dynamic nuclear polarization with 4.7 % and 3 % polarization, respectively. The longitudinal relaxation constants (T1 ) for the labeled acetyl and carboxyl carbonyls were approximately 30 seconds, supporting in vivo imaging and spectroscopy applications. In vitro hydrolysis, transacetylation, and albumin binding of hyperpolarized aspirin were readily monitored in real time by 13 C-NMR spectroscopy. Hyperpolarized, double-labeled aspirin was well tolerated in mice and could be observed by both 13 C-MR imaging and 13 C-NMR spectroscopy in vivo.

Keywords: aspirin; chemopreventive; hyperpolarization; magnetic resonance imaging; magnetic resonance spectroscopy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylation
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Aspirin / chemistry
  • Aspirin / pharmacokinetics*
  • Carbon Isotopes / analysis*
  • Hydrolysis
  • Male
  • Mice
  • Serum Albumin, Bovine / metabolism*
  • Tissue Distribution

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Carbon Isotopes
  • Serum Albumin, Bovine
  • Aspirin