P-31-MRS MEASUREMENTS OF EXTRACELLULAR PH OF TUMORS USING 3-AMINOPROPYLPHOSPHONATE
P-31-MRS MEASUREMENTS OF EXTRACELLULAR PH OF TUMORS USING 3-AMINOPROPYLPHOSPHONATE
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DOI：
10.1152/ajpcell.1994.267.1.c195
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发表时间：
1994-07-01
影响因子：
--
通讯作者：
BHUJWALLA, Z
中科院分区：
文献类型：
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作者：
GILLIES, RJ;LIU, Z;BHUJWALLA, Z
肿瘤的细胞外pH值（pH(ex)）一般呈酸性。然而，直到最近，非侵入性磁共振波谱（MRS）测量才确定，原位肿瘤细胞的细胞内pH值（pH(in)）与正常组织相比是中性或微碱性的。因此，肿瘤组织中的细胞比非肿瘤组织中的细胞保持更大的pH梯度。迄今为止，肿瘤pH值（ex）的测量都是使用微电极进行的，这就排除了在同一制剂中测量pH值（ex）和pH值（in）的可能性。此外，微电极是侵入性的，有可能改变测量的pH值。本通讯描述了在体外生物反应器培养和体内使用3-氨基丙基膦酸盐（3-APP）和无机磷酸盐的P-31-MRS分析同时测量pH（ex）和pH（in）。体外实验结果表明，3-APP无毒，其共振频率对pH值敏感，不受温度和离子强度的显著影响。生物反应器实验表明，该化合物既不被细胞内化也不被细胞代谢。体内实验表明，3-APP可以腹腔给药，RIF-1肿瘤维持7.25的稳态pH值（in）和6.66的稳态pH值（ex）。这些数据对基础肿瘤细胞生理学和癌症化疗和热疗方法的设计具有重要意义，因为这两种方式都表现出pH敏感性。这些技术也可能适用于体内其他器官系统的局部MRS。
The extracellular pH (pH(ex)) of tumors is generally acidic. However, it is only recently that noninvasive magnetic resonance spectroscopic (MRS) measurements have determined that the intracellular pH (pH(in)) of tumor cells in situ is neutral or slightly alkaline compared with that of normal tissues. Thus cells in tumors maintain larger pH gradients than do cells in nontumor tissues. To date, measurements of pH(ex) in tumors have been made using microelectrodes, which preclude measurement of pH(ex) and pH(in) within the same preparation. In addition, microelectrodes are invasive and have the potential to alter the measured pH values. The present communication describes simultaneous measurement of pH(ex) and pH(in) in vitro in bioreactor culture and in vivo using P-31-MRS analyses of 3-aminopropylphosphonate (3-APP) and inorganic phosphate. In vitro results indicate that 3-APP is not toxic and that its resonant frequency is sensitive to pH and not significantly affected by temperature or ionic strength. Bioreactor experiments indicate that this compound is neither internalized nor metabolized by cells. Experiments in vivo indicate that 3-APP can be administered intraperitoneally and that RIF-1 tumors maintain a steady-state pH(in) of 7.25 and a pH(ex) of 6.66. These data have significance to basic tumor cell physiology and to the design of approaches to cancer chemotherapy and hyperthermic therapy, because both of these modalities exhibit pH sensitivity. It is also likely that these techniques will be applicable to localized MRS of other organ systems in vivo.