Measuring Extracellular pH Within Tumors Using CEST MRI

pH是肿瘤发育中的关键微环境因素之一。肿瘤细胞通常被视为高乳酸和h+producers.1细胞外酸中毒通过改变细胞内pH(PHI)来表示对细胞存活的威胁,其中0.1phi变异可以破坏多种生物学功能。2肿瘤细胞外pH(PHE)的测量可用于诊断临床肿瘤以及癌症生物学的临床前研究。yaboapp体育官网弱碱或弱酸药物的疗效可能受肿瘤pHE的影响,并且还可能影响正常的器官。因此,测量肿瘤和正常器官的pHE可以提供预测/评估治疗效果并促进治疗优化的见解。通过多项研究证明了化学交换饱和度转移(CEST)MRI,以追踪肿瘤酸中毒的实用,非侵入性方法。

CEST MRI measures the water signal change after a long, low power RF (radiofrequency) irradiation pulse is applied at a resonance frequency different from water. In CEST imaging, a chemical agent containing protons exchangeable with water is used. When the irradiation pulse is applied at its specific resonance frequency, the detectable magnetization from such a proton is reduced (or “saturated”). Meanwhile, rapid chemical exchange of this proton with a proton in a nearby water molecule occurs, transferring the saturation to the water proton and leading to a reduction in water signal. In an actual experiment, a series of irradiation pulses with different frequency offsets is applied, and a spectrum of normalized water saturation is acquired for analysis. CEST has taken MRI into new territory in which chemical agents with low concentration can be detected. Furthermore, CEST MRI using a variety of contrast agents has been used in clinical and preclinical studies to assist in tumor staging, tumor metabolite imaging, tumor pH imaging, and tumor reporter gene imaging.3.

Fig. 1 – Chemical Structure of Iopamidol

酰胺质子的c效果是依赖于pH值的because the exchange of an amide proton with water is base catalyzed under physiological conditions. The contrast agent we utilize for CEST pH imaging, iopamidol (Isovue, Bracco Imaging) (Fig.1), a clinically approved CT contrast agent, contains amide groups generating two CEST effects at different irradiation frequencies. Their ratio can be used to measure pH in a way that is independent from agent concentration, endogenous T1 relaxation time, and incomplete saturation.4.在A.体内CEST-based pH measurement, we acquire a collection of CEST images (one of them in Fig. 2, left) with a series of predefined frequency offsets, and a CEST spectrum is generated based on a user-defined ROI. Then, 4.2ppm peak and 5.6ppm peak are extracted mathematically (Fig. 2, center) and their amplitudes are used to derive the pH value based on a formula calibrated previously using a phantom with known acidities. In addition to numerical pH readout for the selected ROI, a pH map (Fig. 2, right) is also generated offering pH values spatially distributed at pixel level in the ROI. This may provide useful information in evaluating heterogeneity in tumor acidosis. In this example, since the kidneys are in the same view, the pHe values of the kidneys can also be obtained for evaluation.

图2 - 基于CEST MRI的肿瘤pH分析

景has a high-field strength (7.0T) Bruker Biospec MRI system capable of acquiring high quality images, and an in-house developed program that provides fast and accurate data analysis. We are validating tumor acidosis CEST imaging studies for customers.

Contact us了解有关肿瘤PHE成像的更多信息,并通过这种切割边缘解决方案提前您的肿瘤研究。


参考

1Warburg, O. The Metabolism of Tumors (R.R. Smith, New York, 1931).

2Chiche J,ILC K,LaferrièreJ,猪蹄E,Dayan F,Mazure Nm,Brahimi-Horn Mc,PouysségurJ.缺氧诱导碳酸酐酶IX和XII通过调节细胞内pH调节酸中毒来促进肿瘤细胞生长。癌症res。2009年1月1日; 69(1):358-68。

3.Bokacheva L1,Ackerstaf e,Lekaye HC,Zakian K,Koutcher Ja。高场小动物磁共振肿瘤学研究。物理med biol。2014年1月20日; 59(2):R65-R127。

4.陈LQ,霍姆森·厘米,杰弗瑞JJ,Robey If,Kuo ph,Pagel Md。抗酸碱MRI在体内肿瘤内细胞外pH的评价。汇率。2014年11月72(5):1408-17。

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