A hydrogen peroxide-responsive hyperpolarized 13C MRI contrast agent - PubMed (original) (raw)

. 2011 Mar 23;133(11):3776-9.

doi: 10.1021/ja111589a. Epub 2011 Mar 2.

Affiliations

A hydrogen peroxide-responsive hyperpolarized 13C MRI contrast agent

Alexander R Lippert et al. J Am Chem Soc. 2011.

Abstract

We report a new reaction-based approach for the detection of hydrogen peroxide (H(2)O(2)) using hyperpolarized (13)C magnetic resonance imaging ((13)C MRI) and the H(2)O(2)-mediated oxidation of α-ketoacids to carboxylic acids. (13)C-Benzoylformic acid reacts selectively with H(2)O(2) over other reactive oxygen species to generate (13)C-benzoic acid and can be hyperpolarized using dynamic nuclear polarization, providing a method for dual-frequency detection of H(2)O(2). Phantom images collected using frequency-specific imaging sequences demonstrate the efficacy of this responsive contrast agent to monitor H(2)O(2) at pre-clinical field strengths. The combination of reaction-based detection chemistry and hyperpolarized (13)C MRI provides a potentially powerful new methodology for non-invasive multi-analyte imaging in living systems.

PubMed Disclaimer

Figures

Figure 1

Figure 1

(a) 13C NMR spectra of hyperpolarized 13C-BFA after 21 s of reaction with 10, 100, 250, 500, 750, and 1000 µM H2O2 at 11.7T. Spectra were acquired with a single scan every 3 s with a 5° pulse, except for 10 and 100 µM which were acquired after 21 s with a 90° pulse. (b) Linear correlation of the ratio of integrated peak intensities of the C1 (carboxylate carbon) of 13C-BA to the C1 (carboxylate carbon) of 13C-BFA versus the concentration of H2O2; R2 = 0.988.

Figure 2

Figure 2

Response of 50 µM BFA to various ROS. All ROS were added at 5 mM, except for O2− which was generated enzymatically at a rate of 24 µmol/min for 120 min (2.9 mM total). Concentrations of benzoic acid were measured by HPLC after 0, 5, 10, 15, and 20 min of reaction except for O2− which was measured after 0, 30, 60, 90, and 120 min of reaction.

Figure 3

Figure 3

Phantom images of 5 M thermally polarized 13C-BFA in H2O, 5 M thermally polarized 13C-BA in DMA, and 20 mM hyperpolarized 13C-BFA in 100 mM phosphate, 0.3 mM EDTA buffered at pH 7.8 with 0, 25, 50, 100, and 200 mM H2O2. (a) 1H spin echo image. (b) Frequency specific image with selective excitation of the resonance of 5 M 13C-BA in DMA. (c) Frequency specific image with selective excitation of the resonance of 5 M 13C-BFA in H2O. (d) Frequency specific image with selective excitation of the resonance of 13C-BA buffered at pH 7.8 (e) Frequency specific image with selective excitation of the resonance of 13C-BFA buffered at pH 7.8. Images in (b)–(e) were acquired after ~37 s of reaction with H2O2 with a TR = 150 ms, FOV 40 × 40 × 40 mm, 16 × 12 × 12 matrix and zerofilled to a final resolution of 1.25 mm isotropic.

Scheme 1

Scheme 1

Design of a hyperpolarized 13C MRI contrast agent for detection of H2O2 through H2O2-mediated α-ketoacid oxidative decarboxylation and the synthesis of 13C-BFA and its H2O2-mediated conversion to 13C-BA.

Similar articles

Cited by

References

    1. Rhee SG. Science. 2006;312:1882–1883. - PubMed
    2. Stone JR, Yang S. Antioxid. Redox Signal. 2006;8:243–270. - PubMed
    3. Miller EW, Chang CJ. Curr. Opin. Chem. Biol. 2007;11:620–625. - PMC - PubMed
    4. Winterbourn CC. Nat. Chem. Biol. 2008;4:278–286. - PubMed
    5. Poole LB, Nelson KJ. Curr. Opin. Cell. Biol. 2008;12:18–24. - PMC - PubMed
    6. Paulsen CE, Carroll KS. ACS Chem. Biol. 2010;5:47–62. - PMC - PubMed
    1. Fruehauf JP, Meyskens FL., Jr Clin. Cancer Res. 2007;13:789–794. - PubMed
    2. Finkel T, Serrano M, Blasco MA. Nature. 2007;448:767–774. - PubMed
    3. Ishikawa K, Takenaga K, Akimoto M, Koshikawa N, Yamaguchi A, Imanishi H, Nakada K, Honma Y, Hayashi J. Science. 2008;320:661–664. - PubMed
    1. Mattson MP. Nature. 2004;430:631–639. - PMC - PubMed
    2. Lin MT, Beal MF. Nature. 2006;443:787–795. - PubMed
    3. DiMauro S, Schon EA. Annu. Rev. Neurosci. 2008;31:91–123. - PubMed
    1. Houstis N, Rosen ED, Lander ES. Nature. 2006;440:944–948. - PubMed
    2. Pop-Busui R, Sima A, Stevens M. Diabetes-Metab. Res. Rev. 2006;22:257–273. - PubMed
    3. Jay D, Hitomi H, Griendling KK. Free Radical Biol. Med. 2006;40:183–192. - PubMed
    1. Halliwell B, Whiteman M. Br. J. Pharmacol. 2004;142:231–255. - PMC - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources