Garcia-Martin Maria L, Martinez Gary V, Raghunand Natarajan, Sherry A Dean, Zhang Shanrong, Gillies Robert J
Department of Biochemistry and Molecular Biophysics, Arizona Cancer Center, The University of Arizona, Tucson, AZ 85724-5024, USA.
Magn Reson Med. 2006 Feb;55(2):309-15. doi: 10.1002/mrm.20773.
Previous studies using MR spectroscopy have shown that the extracellular pH (pH(e)) of tumors is acidic compared to normal tissues. This has a number of important sequelae that favor the emergence of more aggressive and therapy-resistant tumors. New MRI methods based on pH-sensitive T1 relaxivity are an attractive alternative to previous spectroscopic methods, as they allow improvements in spatial and temporal resolution. Recently, pH-dependent GdDOTA-4AmP5- and a pH-independent analog, GdDOTP5-, were used to image renal pH in mice. The current study has used a similar approach to image pH(e) in rat gliomas. Significant differences were observed compared to the renal study. First, the relaxivity of GdDOTP5- was found to be affected by the higher extracellular protein content of tumors. Second, the pixel-by-pixel analysis of the GdDOTP5- and GdDOTA-4AmP5- pharmacokinetics showed significant dispersion, likely due to the temporal fluctuations in tumor perfusion. However, there was a robust correlation between the maximal enhancements produced by the two boluses. Therefore, to account for the local time-courses differences, pH(e) maps were calculated at the time of maximal enhancement in each pixel. Finally, the comparison of the pH(e) and the time to maximal intensity maps revealed an inverse relationship between pH(e) and tumor perfusion.
以往使用磁共振波谱的研究表明，与正常组织相比，肿瘤的细胞外pH值（pH(e)）呈酸性。这会产生许多重要的后果，有利于更具侵袭性和抗治疗性肿瘤的出现。基于pH敏感的T1弛豫率的新型磁共振成像方法是以往波谱方法的一个有吸引力的替代方案，因为它们能提高空间和时间分辨率。最近，pH依赖性的钆喷酸葡胺-4-氨基戊酸-5-（GdDOTA-4AmP5）和一种pH非依赖性类似物钆喷替酸葡甲胺-5-（GdDOTP5-）被用于对小鼠肾脏pH进行成像。本研究采用了类似的方法对大鼠胶质瘤中的pH(e)进行成像。与肾脏研究相比，观察到了显著差异。首先，发现GdDOTP5-的弛豫率受肿瘤细胞外蛋白质含量较高的影响。其次，对GdDOTP5-和GdDOTA-4AmP5-药代动力学的逐像素分析显示出显著的离散，这可能是由于肿瘤灌注的时间波动所致。然而，两次团注产生的最大增强之间存在很强的相关性。因此，为了考虑局部时间过程差异，在每个像素最大增强时计算pH(e)图。最后，pH(e)图与最大强度时间图的比较揭示了pH(e)与肿瘤灌注之间的反比关系。
