Estimations of intra- and extracellular volume and pH by 31P magnetic resonance spectroscopy: effect of therapy on RIF-1 tumours.
Estimations of intra- and extracellular volume and pH by 31P magnetic resonance spectroscopy: effect of therapy on RIF-1 tumours.
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DOI：
10.1038/bjc.1998.548
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发表时间：
1998-09
影响因子：
8.8
通讯作者：
Stubbs M
中科院分区：
文献类型：
--
作者：
Bhujwalla ZM;McCoy CL;Glickson JD;Gillies RJ;Stubbs M
要量化活组织中的代谢物或药物浓度，需要测定细胞内和细胞外的体积。本研究通过31P磁共振波谱(31P磁共振波谱)非侵入性地实现这一点，其中二甲基甲基膦酸二甲酯(DMMP)作为总水空间的标记，3-氨基丙基膦(3-APP)作为细胞外空间的标记，P和3-APP分别作为细胞内pH(PH)和细胞外pH(Phe)的标记。用3H2O和[14C]菊糖分别作为细胞外间隙和总间隙的标记物，用经典的放射性标记方法验证了肿瘤体积的MRS测量。放射性标记RIF-1肿瘤细胞外体积分数为23+/-0.83%(平均+/-S.E.M.N=9)，与MRS结果(伦敦27+/-2.9%，n=9，巴尔的摩35+/-6.7，n=14)无显著差异(P>；0.1)。在未经治疗的RIF-1肿瘤中，pH比Phe高约0.2个单位(P<；0.01)。5-氟尿嘧啶(5FU)(165 mg kg(-1))处理后，Phe和细胞外体积百分比均无明显变化。然而，治疗后48h的pH显著升高(P<；0.01)与肿瘤体积的减小和生物能量状态的改善[NTP/无机磷(PI)比率]相关。这项研究表明，用MR方法(通过“金标准”验证)来研究药物治疗对体内实体瘤细胞内外间隙和pH的影响是可行的。
Quantification of metabolite or drug concentrations in living tissues requires determination of intra- and extracellular volumes. This study demonstrates how this can be achieved non-invasively by 31P magnetic resonance spectroscopy (MRS) employing dimethyl methylphosphonate (DMMP) as a marker of total water space, 3-aminopropylphosphonate (3-APP) as a marker of extracellular space and P and 3-APP as markers of intracellular pH (pH) and extracellular pH (pHe) respectively. The MRS measurements of the tumour volumes were validated by classic radiolabelling methods using 3H2O and [14C]inulin as markers of total and extracellular space respectively. The extracellular volume fraction measured by radiolabelling of RIF-1 tumours was 23 +/- 0.83% (mean +/- s.e.m. n = 9), not significantly different (P > 0.1) from that found by MRS (27 +/- 2.9%, n = 9, London, and 35 +/- 6.7, n = 14, Baltimore). In untreated RIF-1 tumours, pH was about 0.2 units higher than pHe (P < 0.01). 5-Fluorouracil (5FU) treatment (165 mg kg(-1)) caused no significant changes in either pHe or per cent extracellular volume. However significant increases in pH, 48 h after treatment (P < 0.01) correlated with decreased tumour size and improved bioenergetic status [NTP/inorganic phosphate (Pi) ratio]. This study shows the feasibility of an MR method (verified by a 'gold standard') for studying the effects of drug treatment on intra- and extracellular spaces and pH in solid tumours in vivo.