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基于 microPET/MR 平台的五个鼻咽癌动物模型的纵向评估。

Longitudinal evaluation of five nasopharyngeal carcinoma animal models on the microPET/MR platform.

机构信息

Department of Diagnostic Radiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

出版信息

Eur J Nucl Med Mol Imaging. 2022 Apr;49(5):1497-1507. doi: 10.1007/s00259-021-05633-4. Epub 2021 Dec 4.

Abstract

PURPOSE

We longitudinally evaluated the tumour growth and metabolic activity of three nasopharyngeal carcinoma (NPC) cell line models (C666-1, C17 and NPC43) and two xenograft models (Xeno76 and Xeno23) using a micropositron emission tomography and magnetic resonance (microPET/MR). With a better understanding of the interplay between tumour growth and metabolic characteristics of these NPC models, we aim to provide insights for the selection of appropriate NPC cell line/xenograft models to assist novel drug discovery and evaluation.

METHODS

Mice were imaged by F-deoxyglucose ([F]FDG) microPET/MR twice a week for consecutive 3-7 weeks. [F]FDG uptake was quantified by standardized uptake value (SUV) and presented as SUVmean tumour-to-liver ratio (SUVRmean). Longitudinal tumour growth patterns and metabolic patterns were recorded. SUVRmean and histological characteristics were compared across the five NPC models. Cisplatin was administrated to one selected optimal tumour model, C17, to evaluate our imaging platform.

RESULTS

We found variable tumour growth and metabolic patterns across different NPC tumour types. C17 has an optimal growth rate and higher tumour metabolic activity compared with C666-1. C666-1 has a fast growth rate but is low in SUVRmean at endpoint due to necrosis as confirmed by H&E. NPC43 and Xeno76 have relatively slow growth rates and are low in SUVRmean, due to severe necrosis. Xeno23 has the slowest growth rate, and a relative high SUVRmean. Cisplatin showed the expected therapeutic effect in the C17 model in marked reduction of tumour size and metabolism.

CONCLUSION

Our study establishes an imaging platform that characterizes the growth and metabolic patterns of different NPC models, and the platform is well able to demonstrate drug treatment outcome supporting its use in novel drug discovery and evaluation for NPC.

摘要

目的

我们使用微正电子发射断层扫描和磁共振(microPET/MR)对三种鼻咽癌(NPC)细胞系模型(C666-1、C17 和 NPC43)和两种异种移植模型(Xeno76 和 Xeno23)的肿瘤生长和代谢活性进行了纵向评估。通过更好地了解这些 NPC 模型的肿瘤生长和代谢特征之间的相互作用,我们旨在为选择合适的 NPC 细胞系/异种移植模型提供见解,以辅助新型药物的发现和评估。

方法

连续 3-7 周,每周两次对小鼠进行 F-脱氧葡萄糖([F]FDG) microPET/MR 成像。通过标准化摄取值(SUV)定量[F]FDG 摄取,并以肿瘤与肝脏的 SUV 均值比(SUVmean 肿瘤与肝脏比,SUVRmean)表示。记录肿瘤生长模式和代谢模式的纵向变化。比较五种 NPC 模型之间的 SUVRmean 和组织学特征。向一种选定的最佳肿瘤模型 C17 中给予顺铂,以评估我们的成像平台。

结果

我们发现不同 NPC 肿瘤类型之间存在不同的肿瘤生长和代谢模式。C17 的生长速度较快,肿瘤代谢活性较高,与 C666-1 相比。C666-1 的生长速度较快,但由于坏死,终点时 SUVRmean 较低,这一点通过 H&E 得到证实。NPC43 和 Xeno76 的生长速度相对较慢,SUVRmean 较低,这是由于严重坏死所致。Xeno23 的生长速度最慢,SUVRmean 相对较高。顺铂在 C17 模型中显示出预期的治疗效果,肿瘤大小和代谢明显减少。

结论

我们的研究建立了一个成像平台,该平台可描述不同 NPC 模型的生长和代谢模式,该平台能够很好地展示药物治疗效果,支持其在 NPC 新型药物发现和评估中的应用。

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