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放射性标记的蛋氨酸、胆碱和氟脱氧葡萄糖在人星形细胞瘤中的摄取与掺入的比较研究。

A comparative study on the uptake and incorporation of radiolabeled methionine, choline and fluorodeoxyglucose in human astrocytoma.

作者信息

Narayanan T K, Said Sinan, Mukherjee Jogeshwar, Christian Brad, Satter Martin, Dunigan Kelly, Shi Bing, Jacobs Martin, Bernstein Theodore, Padma Madakasira, Mantil Joseph

机构信息

Wallace Kettering Neuroscience Institute and Department of Nuclear Medicine/PET, Kettering Medical Center, Dayton, OH 45429, USA.

出版信息

Mol Imaging Biol. 2002 Mar;4(2):147-56. doi: 10.1016/s1536-1632(01)00010-5.

DOI:10.1016/s1536-1632(01)00010-5
PMID:14537137
Abstract

PURPOSE

The goal of this investigation was to evaluate uptake and incorporation of 2-deoxy-2-[18F]fluoro-D-glucose (FDG), 11C-methionine, and 11C-choline in 17 patients suspected of grade-II and grade-III tumors using positron emission tomography (PET) and use in vitro astrocytoma cell lines in order to support in vivo findings.

METHODS

Seventeen patients with suspected astrocytomas (9 grade-II and 8 grade-III) were studied by PET with FDG and 11C-methionine; and one patient (grade-III) with FDG, 11C-methionine and 11C-choline. Uptake of PET molecular imaging probe was quantitative based on tumor to corresponding contralateral-region uptake ratio, tumor to mean-cortical-uptake ratio, and tumor to white matter uptake ratio. This was correlated with World Health Organization histology grading system and clinical follow-up. Uptake and incorporation of 3H-methionine, 3H-choline and FDG into lipid, RNA, DNA, and protein were investigated in a grade-III human tumor brain-14 astrocytoma cell line.

RESULTS

A time-dependent increase in the total uptake of 3H-methionine, 3H-choline and FDG was observed in human tumor brain-14 astrocytoma-III cell line. 3H-methionine was incorporated predominantly into proteins (in excess of 40% at 1 h) while 3H-choline incorporated primarily into lipids (in excess of 60% at 1 hr). Total uptake of FDG was accounted for in the free-pool supernatant fraction. In all patients, PET images of 11C-methionine and FDG provided higher tumor to white matter ratios than tumor to corresponding contra-lateral region ratios and tumor to mean cortical uptake ratios. In grade II patients, FDG did not exhibit significant increase in tumor uptake, while 11C-methionine was a good predictor with ratios of approximately 1.50 +/- 0.48. In grade III patients, both FDG and 11C-methionine exhibited higher ratios than for grade II, with 11C-methionine being the greatest (ratios of 2.50 +/- 0.85), possibly suggesting enhanced protein synthesis. With respect to tumor delineating potential, 11C-choline may be equal to or slightly better than 11C-methionine in the subject evaluated with all three probes.

CONCLUSIONS

Results suggest that a combination of FDG and 11C-methionine is useful in the prediction of histological grade of astrocytomas. In addition, 11C-methionine is better than FDG in delineating tumor boundary for low-grade gliomas. In vitro results suggest that 3H-methionine is significantly incorporated into proteins and provides the major driving force in the uptake of 11C-methionine observed in PET images.

摘要

目的

本研究的目的是使用正电子发射断层扫描(PET)评估17例疑似II级和III级肿瘤患者对2-脱氧-2-[18F]氟-D-葡萄糖(FDG)、11C-蛋氨酸和11C-胆碱的摄取和掺入情况,并使用体外星形细胞瘤细胞系以支持体内研究结果。

方法

对17例疑似星形细胞瘤患者(9例II级和8例III级)进行了FDG和11C-蛋氨酸PET研究;对1例III级患者进行了FDG、11C-蛋氨酸和11C-胆碱PET研究。基于肿瘤与相应对侧区域摄取比、肿瘤与平均皮质摄取比以及肿瘤与白质摄取比,对PET分子成像探针的摄取进行定量分析。这与世界卫生组织组织学分级系统及临床随访相关。在III级人肿瘤脑-14星形细胞瘤细胞系中研究了3H-蛋氨酸、3H-胆碱和FDG在脂质、RNA、DNA和蛋白质中的摄取及掺入情况。

结果

在人肿瘤脑-14星形细胞瘤-III细胞系中观察到3H-蛋氨酸、3H-胆碱和FDG的总摄取随时间增加。3H-蛋氨酸主要掺入蛋白质中(1小时时超过40%),而3H-胆碱主要掺入脂质中(1小时时超过60%)。FDG的总摄取在游离池上清部分中体现。在所有患者中,11C-蛋氨酸和FDG的PET图像显示肿瘤与白质的比值高于肿瘤与相应对侧区域的比值以及肿瘤与平均皮质摄取的比值。在II级患者中,FDG的肿瘤摄取未显著增加,而11C-蛋氨酸是一个良好的预测指标,比值约为1.50±0.48。在III级患者中,FDG和11C-蛋氨酸的比值均高于II级患者,其中11C-蛋氨酸的比值最大(为2.50±0.85),这可能提示蛋白质合成增强。就肿瘤勾画潜力而言,在使用所有三种探针评估的受试者中,11C-胆碱可能与11C-蛋氨酸相当或略优于11C-蛋氨酸。

结论

结果表明,FDG和11C-蛋氨酸联合使用有助于预测星形细胞瘤的组织学分级。此外,在勾画低级别胶质瘤的肿瘤边界方面,11C-蛋氨酸优于FDG。体外研究结果表明,3H-蛋氨酸显著掺入蛋白质中,并为PET图像中观察到的11C-蛋氨酸摄取提供了主要驱动力。

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