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应用 1H-MR 波谱和 18F-FDG PET 成像对荷肝癌大鼠进行多模态体内代谢评估。

Multimodal assessment of in vivo metabolism with hyperpolarized [1-13C]MR spectroscopy and 18F-FDG PET imaging in hepatocellular carcinoma tumor-bearing rats.

机构信息

GE Global Research, Munich, Germany.

出版信息

J Nucl Med. 2013 Jul;54(7):1113-9. doi: 10.2967/jnumed.112.110825. Epub 2013 Apr 17.

DOI:10.2967/jnumed.112.110825
PMID:23596002
Abstract

UNLABELLED

Abnormalities of tumor metabolism can be exploited for molecular imaging. PET imaging of (18)F-FDG is a well-established method using the avid glucose uptake of tumor cells. (13)C MR spectroscopic imaging (MRSI) of hyperpolarized [1-(13)C]pyruvate and its metabolites, meanwhile, represents a new method to study energy metabolism by visualizing, for example, the augmented lactate dehydrogenase activity in tumor cells. Because of rapid signal loss, this method underlies strict temporal limitations, and the acquisition of data-encoding spatial, temporal, and spectral information within this time frame-is challenging. The object of our study was to compare spectroscopic images with (18)F-FDG PET images for visualizing tumor metabolism in a rat model.

METHODS

(13)C MRSI with IDEAL (Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation) chemical shift imaging in combination with single-shot spiral acquisition was used to obtain dynamic data from 23 rats bearing a subcutaneous hepatocellular carcinoma and from reference regions of the same animals. Static and dynamic analysis of (18)F-FDG PET images of the same animals was performed. The data were analyzed qualitatively (visual assessment) and quantitatively (magnitude and dynamics of (18)F-FDG uptake, (13)C MRSI dynamics, and physiologic parameters).

RESULTS

In most animals increased [1-(13)C]lactate signals in the tumor could be detected by simple display of integrated [1-(13)C]lactate images with corresponding enhanced (18)F-FDG uptake. Low [1-(13)C]pyruvate or [1-(13)C]lactate signals did not correlate with histologic or physiologic parameters. Significantly less pyruvate reached the tumors than the gastrointestinal tract, but in tumors a significantly higher amount of pyruvate was converted to lactate and alanine within seconds after intravenous administration.

CONCLUSION

This study reveals that PET and (13)C MRSI can be used to visualize increased glycolytic flux in malignant tissue. The combination of signals will allow the quantitative dissection of substrate metabolism, with respect to uptake and downstream metabolic pathways. Although hyperpolarized [1-(13)C]pyruvate increases the sensitivity of MR imaging, signal-to-noise ratio constraints still apply for spatially and temporally resolved (13)C MRSI, emphasizing the need for further MR methodologic development. These first imaging data suggest the feasibility of (13)C MRSI for future clinical use.

摘要

目的

比较光谱图像与(18)F-FDG PET 图像,以可视化大鼠模型中的肿瘤代谢。

方法

使用 IDEAL(水和脂肪的迭代分解与回波不对称和最小二乘法估计)化学位移成像结合单次螺旋采集的(13)C MRSI 从 23 只荷皮下肝癌大鼠和同一动物的参考区域获得动态数据。对同一动物的(18)F-FDG PET 图像进行静态和动态分析。对数据进行定性(视觉评估)和定量((18)F-FDG 摄取的幅度和动力学、(13)C MRSI 动力学和生理参数)分析。

结果

在大多数动物中,通过简单显示具有相应增强(18)F-FDG 摄取的整合[1-(13)C]乳酸图像,可以检测到肿瘤中增加的[1-(13)C]乳酸信号。低[1-(13)C]丙酮酸或[1-(13)C]乳酸信号与组织学或生理参数无关。与胃肠道相比,到达肿瘤的丙酮酸明显较少,但在肿瘤中,静脉注射后几秒钟内,丙酮酸转化为乳酸和丙氨酸的量明显增加。

结论

本研究表明,PET 和(13)C MRSI 可用于可视化恶性组织中糖酵解通量的增加。信号的组合将允许对摄取和下游代谢途径的底物代谢进行定量分析。尽管极化[1-(13)C]丙酮酸增加了磁共振成像的灵敏度,但对于空间和时间分辨的(13)C MRSI,信噪比限制仍然适用,这强调了进一步开发磁共振方法的必要性。这些初步的成像数据表明(13)C MRSI 未来临床应用的可行性。

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