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.
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DOI：
10.1021/ac402230h
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发表时间：
2014-01-21
影响因子：
7.4
通讯作者：
Khramtsov, Valery V.
中科院分区：
文献类型：
--
作者：
Samouilov, Alexandre;Efimoya, Olga V.;Bobko, Andrey A.;Sun, Ziqi;Petryakov, Sergey;Eubank, Timothy D.;Trofimov, Dmitrii G.;Kirilyuk, Igor A.;Grigor'ev, Igor A.;Takahashi, Wataru;Zweier, Jay L.;Khramtsov, Valery V.
最近已经开发了用于水性样品的pH绘图的可变射频质子-电子双共振成像（VRF PEDRI）方法（Efimova等人，J. Magn. Reson. 2011，209，227-232）。从质子化和非质子化形式的pH敏感探针的电子顺磁共振（EPR）频率下进行的两次PEDRI采集中提取pH图。为了将VRF PEDRI转化为体内环境，合成了先进的pH探针。探头氘化导致在一个狭窄的光谱线1.2 G相比，允许增加的Overhauser增强和减少射频功率沉积的nondeuterated模拟线宽度为2.1 G。探针与细胞不可渗透的三肽谷胱甘肽（GSH）的结合允许靶向细胞外组织空间，用于监测细胞外肿瘤酸中毒，这是肿瘤病理生理学中的一个预后因素。该探针表现出在5.8-7.8范围内的pH灵敏度，最适合于测量酸性细胞外肿瘤pH（pHe）。在携带Met-1肿瘤的小鼠上进行体内VRF PEDRI。与中性平均pHe（7.1 ± 0.1）的正常乳腺相比，我们观察到肿瘤组织中酸性平均pHe（6.8 ± 0.1）的更宽pH分布。总之，VRF PEDRI结合新开发的pH探针提供了一种分析方法，用于空间分辨的非侵入性pHe监测，在体内。
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 (pHe). In vivo VRF PEDRI was performed on Met-1 tumor-bearing mice. Compared to normal mammary glands with a neutral mean pHe (7.1 ± 0.1), we observed broader pH distribution with acidic mean pHe (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 pHe monitoring, in vivo.
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影响因子：
2.8
作者：
KHRAMTSOV, VV;WEINER, LM;VOLODARSKY, LB
通讯作者：
VOLODARSKY, LB
影响因子：
3
作者：
Kraut, Jeffrey A.;Madias, Nicolaos E.
通讯作者：
Madias, Nicolaos E.
影响因子：
1
作者：
Bobko, A. A.;Kirilyuk, I. A.;Gritsan, N. P.;Polovyanenko, D. N.;Grigor'ev, I. A.;Khramtsov, V. V.;Bagryanskaya, E. G.
通讯作者：
Bagryanskaya, E. G.
影响因子：
2.2
作者：
Khramtsov, Valery V.;Caia, George L.;Samouilov, Alexandre
通讯作者：
Samouilov, Alexandre
影响因子：
3.3
作者：
Foster, MA;Grigor'ev, IA;Nicholson, I
通讯作者：
Nicholson, I