Interstitial pH and pO(2) gradients in solid tumors in vivo: High-resolution measurements reveal a lack of correlation
Interstitial pH and pO(2) gradients in solid tumors in vivo: High-resolution measurements reveal a lack of correlation
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DOI：
10.1038/nm0297-177
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发表时间：
1997-02-01
期刊：
影响因子：
82.9
通讯作者：
Jain, RK
中科院分区：
文献类型：
--
作者：
Helmlinger, G;Yuan, F;Jain, RK
氧分压(Po(2))和pH在肿瘤生物学和治疗中起着至关重要的作用。在此，我们首次使用荧光比率成像和磷光猝灭显微镜对人肿瘤移植瘤中相邻血管之间的间质pH和Po(2)分布进行了高分辨率(小于或等于10微米)的联合测量。我们发现(1)pH和Po(2)曲线形状的异质性；(2)局部pH曲线和相应的Po(2)曲线之间的关系不协调，但平均pH和Po(2)曲线之间有很强的相关性；(3)血管周围的pH/Po(2)和最近的血管血流之间没有相关性；(4)充盈的肿瘤血管是低氧的，因此周围间质中有大量的缺氧区。这种体内微环境的多参数测量为肿瘤的生物过程及其对治疗的反应提供了独特的见解。
The partial pressure of oxygen (pO(2)) and pH play critical roles in tumor biology and therapy. We report here the first combined, high-resolution (less than or equal to 10 mu m) measurements of interstitial pH and pO(2) profiles between adjacent vessels in a human tumor xenograft, using fluorescence ratio imaging and phosphorescence quenching microscopy. We found (1) heterogeneity in shapes of pH and pO(2) profiles; (2) a discordant relation between local pH profiles and corresponding pO(2) profiles, yet a strong correlation between mean pH and pO(2) profiles; (3) no correlation between perivascular pH/pO(2) and nearest vessel blood flow; and (4) well-perfused tumor vessels that were hypoxic and, consequently, large hypoxic areas in the surrounding interstitium. Such multiparameter measurements of the in vivo microenvironment provide unique insights into biological processes in tumors and their response to treatment.