In Vivo Proton-Electron Double-Resonance Imaging of Extracellular Tumor pH Using an Advanced Nitroxide Probe

In Vivo Proton-Electron Double-Resonance Imaging of Extracellular Tumor pH Using an Advanced Nitroxide Probe Full article

Journal

Analytical Chemistry
ISSN: 0003-2700 , E-ISSN: 1520-6882

Output data

Year: 2014, Volume: 86, Number: 2, Pages: 1045-1052 Pages count : DOI: 10.1021/ac402230h

Authors

Samouilov Alexandre ^1,3 , Efimova Olga V. ¹ , Bobko Andrey A. ^1,2 , Sun Ziqi ¹ , Petryakov Sergey ¹ , Eubank Timothy D. ^1,2 , Trofimov Dmitrii G. ⁴ , Kirilyuk Igor A. ⁴ , Grigor'ev Igor A. ⁴ , Takahashi Wataru ^5,1 , Zweier Jay L. ^1,3 , Khramtsov Valery V. ^1,2

Affiliations

1	(Данные Web of science) Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA
2	(Данные Web of science) Ohio State Univ, Dept Internal Med, Div Pulm Allergy Crit Care & Sleep Med, Columbus, OH 43210 USA
3	(Данные Web of science) Ohio State Univ, Dept Internal Med, Div Cardiovasc Med, Columbus, OH 43210 USA
4	(Данные Web of science) Vorozhtsov Inst Organ Chem, Novosibirsk 630090, Russia
5	(Данные Web of science) Hokkaido Univ, Sapporo, Hokkaido 0600814, Japan

A variable radio frequency proton-electron double-resonance imaging (VRF PEDRI) approach for pH mapping of aqueous samples has been recently developed (Efimova et al. J. Magn. Reson. 2011, 209, 227-232). A pH map is extracted from two PEDRI acquisitions performed at electron paramagnetic resonance (EPR) frequencies of protonated and unprotonated forms of a pH-sensitive probe. To translate VRF PEDRI to an in vivo setting, an advanced pH probe was synthesized. Probe deuteration resulted in a narrow spectral line of 1.2 G compared to a nondeuterated analogue line width of 2.1 G allowing for an increase of Overhauser enhancements and reduction in rf power deposition. Binding of the probe to the cell-impermeable tripeptide, glutathione (GSH), allows for targeting to extracellular tissue space for monitoring extracellular tumor acidosis, a prognostic factor in tumor pathophysiology. The probe demonstrated pH sensitivity in the 5.8-7.8 range, optimum for measurement of acidic extracellular tumor pH (pH(e)). In vivo VRF PEDRI was performed on Met-1 tumor-bearing mice. Compared to normal mammary glands with a neutral mean pH(e) (7.1 +/- 0.1), we observed broader pH distribution with acidic mean pH(e) (6.8 +/- 0.1) in tumor tissue. In summary, VRF PEDRI in combination with a newly developed pH probe provides an analytical approach for spatially resolved noninvasive pH(e) monitoring, in vivo.

Samouilov A. , Efimova O.V. , Bobko A.A. , Sun Z. , Petryakov S. , Eubank T.D. , Trofimov D.G. , Kirilyuk I.A. , Grigor'ev I.A. , Takahashi W. , Zweier J.L. , Khramtsov V.V.
In Vivo Proton-Electron Double-Resonance Imaging of Extracellular Tumor pH Using an Advanced Nitroxide Probe

Analytical Chemistry. 2014. V.86. N2. P.1045-1052. DOI: 10.1021/ac402230h WOS Scopus РИНЦ

Full text from publisher

Published online:	Jan 6, 2014
Published print:	Jan 21, 2014

Web of science	WOS:000330204500013
Scopus	2-s2.0-84892712568
Elibrary	21863296
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