Bioconjugate Chemistry
Communication
Cancer Using Hyperpolarized 1-C-13 Pyruvate. Sci. Transl. Med. 5,
198ra108.
ASSOCIATED CONTENT
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S
* Supporting Information
(13) Mugler, J. P., and Altes, T. A. (2013) Hyperpolarized 129Xe MRI
of the human lung. J. Magn. Reson. Imaging 37, 313−331.
(14) Cudalbu, C., Comment, A., Kurdzesau, F., van Heeswijk, R. B.,
Uffmann, K., Jannin, S., Denisov, V., Kirik, D., and Gruetter, R. (2010)
Feasibility of in vivo N-15 MRS detection of hyperpolarized N-15
labeled choline in rats. Phys. Chem. Chem. Phys. 12, 5818−5823.
(15) Nonaka, H., Hata, R., Doura, T., Nishihara, T., Kumagai, K.,
Akakabe, M., Tsuda, M., Ichikawa, K., and Sando, S. (2013) A platform
for designing hyperpolarized magnetic resonance chemical probes.
Nat. Commun. 4, 2411.
The Supporting Information is available free of charge on the
Experimental details; NMR spectra; HR-MS spectra
AUTHOR INFORMATION
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Corresponding Authors
(16) Adams, R. W., Aguilar, J. A., Atkinson, K. D., Cowley, M. J.,
Elliott, P. I. P., Duckett, S. B., Green, G. G. R., Khazal, I. G., Lopez-
Serrano, J., and Williamson, D. C. (2009) Reversible Interactions with
para-Hydrogen Enhance NMR Sensitivity by Polarization Transfer.
Science 323, 1708−1711.
(17) Shchepin, R. V., Truong, M. L., Theis, T., Coffey, A. M., Shi, F.,
Waddell, K. W., Warren, W. S., Goodson, B. M., and Chekmenev, E. Y.
(2015) Hyperpolarization of “Neat” Liquids by NMR Signal
Amplification by Reversible Exchange. J. Phys. Chem. Lett. 6, 1961−
1967.
(18) Theis, T., Truong, M. L., Coffey, A. M., Shchepin, R. V.,
Waddell, K. W., Shi, F., Goodson, B. M., Warren, W. S., and
Chekmenev, E. Y. (2015) Microtesla SABRE Enables 10% Nitrogen-
15 Nuclear Spin Polarization. J. Am. Chem. Soc. 137, 1404−1407.
(19) Truong, M. L., Theis, T., Coffey, A. M., Shchepin, R. V.,
Waddell, K. W., Shi, F., Goodson, B. M., Warren, W. S., and
Chekmenev, E. Y. (2015) 15N Hyperpolarization By Reversible
Exchange Using SABRE-SHEATH. J. Phys. Chem. C 119, 8786−8797.
(20) Zhivonitko, V. V., Skovpin, I. V., and Koptyug, I. V. (2015)
Strong 31P nuclear spin hyperpolarization produced via reversible
chemical interaction with parahydrogen. Chem. Commun. 51, 2506−
2509.
(21) Theis, T., Truong, M., Coffey, A. M., Chekmenev, E. Y., and
Warren, W. S. (2014) LIGHT-SABRE enables efficient in-magnet
catalytic hyperpolarization. J. Magn. Reson. 248, 23−26.
(22) Pravdivtsev, A. N., Yurkovskaya, A. V., Vieth, H.-M., and Ivanov,
K. L. (2014) Spin mixing at level anti-crossings in the rotating frame
makes high-field SABRE feasible. Phys. Chem. Chem. Phys. 16, 24672−
24675.
(23) Whaley, T. W., and Ott, D. G. (1974) Syntheses with stable
isotopes: Pyridine-15N. J. Labelled Compd. 10, 283−286.
(24) Jiang, W., Lumata, L., Chen, W., Zhang, S., Kovacs, Z., Sherry, A.
D., and Khemtong, C. (2015) Hyperpolarized 15N-pyridine Derivatives
as pH-Sensitive MRI Agents. Sci. Rep. 5, 9104.
(25) Hata, R., Nonaka, H., Takakusagi, Y., Ichikawa, K., and Sando, S.
(2015) Design of a hyperpolarized 15N NMR probe that induces a
large chemical-shift change upon binding of calcium ions. Chem.
Commun. 51, 12290−12292.
(26) Bergmann, F., and Wislicki, L. (1953) The Pharmacological
Effects of Massive Doses of Nicotinamide. Br. J. Pharmacol. Chemother.
8, 49−53.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This work was supported by NSF under grant CHE-1416268,
NIH 1R21EB018014 and 1R21EB020323, DOD CDMRP BRP
W81XWH-12-1-0159/BC112431, and Exxon Mobil Knowl-
edge Build.
REFERENCES
■
(1) Nikolaou, P., Goodson, B. M., and Chekmenev, E. Y. (2015)
NMR Hyperpolarization Techniques for Biomedicine. Chem. - Eur. J.
21, 3156−3166.
(2) Green, R. A., Adams, R. W., Duckett, S. B., Mewis, R. E.,
Williamson, D. C., and Green, G. G. R. (2012) The theory and
practice of hyperpolarization in magnetic resonance using para-
hydrogen. Prog. Nucl. Magn. Reson. Spectrosc. 67, 1−48.
(3) Goodson, B. M. (2002) Nuclear magnetic resonance of laser-
polarized noble gases in molecules, materials, and organisms. J. Magn.
Reson. 155, 157−216.
(4) Brindle, K. M. (2015) Imaging Metabolism with Hyperpolarized
13C-Labeled Cell Substrates. J. Am. Chem. Soc. 137, 6418−6427.
(5) Kurhanewicz, J., Vigneron, D. B., Brindle, K., Chekmenev, E. Y.,
Comment, A., Cunningham, C. H., DeBerardinis, R. J., Green, G. G.,
Leach, M. O., Rajan, S. S., et al. (2011) Analysis of Cancer Metabolism
by Imaging Hyperpolarized Nuclei: Prospects for Translation to
Clinical Research. Neoplasia 13, 81−97.
(6) Comment, A., and Merritt, M. E. (2014) Hyperpolarized
Magnetic Resonance as a Sensitive Detector of Metabolic Function.
Biochemistry 53, 7333−7357.
(7) Ardenkjaer-Larsen, J. H., Fridlund, B., Gram, A., Hansson, G.,
Hansson, L., Lerche, M. H., Servin, R., Thaning, M., and Golman, K.
(2003) Increase in signal-to-noise ratio of > 10,000 times in liquid-
state NMR. Proc. Natl. Acad. Sci. U. S. A. 100, 10158−10163.
(8) Day, S. E., Kettunen, M. I., Gallagher, F. A., Hu, D. E., Lerche, M.,
Wolber, J., Golman, K., Ardenkjaer-Larsen, J. H., and Brindle, K. M.
(2007) Detecting tumor response to treatment using hyperpolarized
C-13 magnetic resonance imaging and spectroscopy. Nat. Med. 13,
1382−1387.
(9) Golman, K., Axelsson, O., Johannesson, H., Mansson, S.,
Olofsson, C., and Petersson, J. S. (2001) Parahydrogen-induced
polarization in imaging: Subsecond C-13 angiography. Magn. Reson.
Med. 46, 1−5.
(27) Guyton, J. R., Blazing, M. A., Hagar, J., et al. (2000) Extended-
release niacin vs gemfibrozil for the treatment of low levels of high-
density lipoprotein cholesterol. Arch. Intern. Med. 160, 1177−1184.
(28) Libri, V., Yandim, C., Athanasopoulos, S., Loyse, N., Natisvili,
T., Law, P. P., Chan, P. K., Mohammad, T., Mauri, M., and Tam, K. T.
(2014) Epigenetic and neurological effects and safety of high-dose
nicotinamide in patients with Friedreich’s ataxia: an exploratory, open-
label, dose-escalation study. Lancet 384, 504−513.
(29) Mishkovsky, M., Comment, A., and Gruetter, R. (2012) In vivo
detection of brain Krebs cycle intermediate by hyperpolarized
magnetic resonance. J. Cereb. Blood Flow Metab. 32, 2108−2113.
(30) Truong, M. L., Coffey, A. M., Shchepin, R. V., Waddell, K. W.,
and Chekmenev, E. Y. (2014) Sub-second Proton Imaging of 13C
Hyperpolarized Contrast Agents in Water. Contrast Media Mol.
Imaging 9, 333−341.
(10) Golman, K., in’t Zandt, R., and Thaning, M. (2006) Real-time
metabolic imaging. Proc. Natl. Acad. Sci. U. S. A. 103, 11270−11275.
(11) Branca, R. T., He, T., Zhang, L., Floyd, C. S., Freeman, M.,
White, C., and Burant, A. (2014) Detection of brown adipose tissue
and thermogenic activity in mice by hyperpolarized xenon MRI. Proc.
Natl. Acad. Sci. U. S. A. 111, 18001−18006.
(12) Nelson, S. J., Kurhanewicz, J., Vigneron, D. B., Larson, P. E. Z.,
Harzstark, A. L., Ferrone, M., van Criekinge, M., Chang, J. W., Bok, R.,
Park, I., et al. (2013) Metabolic Imaging of Patients with Prostate
D
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