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在结直肠癌肝转移实验大鼠模型中，用[F]氟代胸苷正电子发射断层扫描（PET）和扩散加权磁共振成像（MRI）进行细胞毒性5-氟尿嘧啶治疗后的反应监测

Response Monitoring with [F]FLT PET and Diffusion-Weighted MRI After Cytotoxic 5-FU Treatment in an Experimental Rat Model for Colorectal Liver Metastases.

作者信息

Heskamp Sandra, Heijmen Linda, Gerrits Danny, Molkenboer-Kuenen Janneke D M, Ter Voert Edwin G W, Heinzmann Kathrin, Honess Davina J, Smith Donna-Michelle, Griffiths John R, Doblas Sabrina, Sinkus Ralph, Laverman Peter, Oyen Wim J G, Heerschap Arend, Boerman Otto C

机构信息

Department of Radiology and Nuclear Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.

Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.

出版信息

Mol Imaging Biol. 2017 Aug;19(4):540-549. doi: 10.1007/s11307-016-1021-2.

DOI:10.1007/s11307-016-1021-2
PMID:27798786
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5498638/
Abstract

PURPOSE

The aim of the study was to investigate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and 3'-dexoy-3'-[F]fluorothymidine ([F]FLT) positron emission tomography (PET) as early biomarkers of treatment response of 5-fluorouracil (5-FU) in a syngeneic rat model of colorectal cancer liver metastases.

PROCEDURES

Wag/Rij rats with intrahepatic syngeneic CC531 tumors were treated with 5-FU (15, 30, or 60 mg/kg in weekly intervals). Before treatment and at days 1, 3, 7, and 14 after treatment rats underwent DW-MRI and [F]FLT PET. Tumors were analyzed immunohistochemically for Ki67, TK1, and ENT1 expression.

RESULTS

5-FU inhibited the growth of CC531 tumors in a dose-dependent manner. Immunohistochemical analysis did not show significant changes in Ki67, TK1, and ENT1 expression. However, [F]FLT SUV and SUV were significantly increased at days 4 and 7 after treatment with 5-FU (60 mg/kg) and returned to baseline at day 14 (SUV at days -1, 4, 7, and 14 was 1.1 ± 0.1, 2.3 ± 0.5, 2.3 ± 0.6, and 1.5 ± 0.4, respectively). No changes in [F]FLT uptake were observed in the nontreated animals. Furthermore, the apparent diffusion coefficient (ADC) did not change in 5-FU-treated rats compared to untreated rats.

CONCLUSION

This study suggests that 5-FU treatment induces a flare in [F]FLT uptake of responsive CC531 tumors in the liver, while the ADC did not change significantly. Future studies in larger groups are warranted to further investigate whether [F]FLT PET can discriminate between disease progression and treatment response.

摘要

目的

本研究旨在探讨扩散加权磁共振成像（DW-MRI）和3'-脱氧-3'-[F]氟胸苷（[F]FLT）正电子发射断层扫描（PET）作为5-氟尿嘧啶（5-FU）对同基因大鼠结直肠癌肝转移治疗反应早期生物标志物的潜力。

程序

对患有肝内同基因CC531肿瘤的Wag/Rij大鼠给予5-FU治疗（每周一次，剂量为15、30或60mg/kg）。在治疗前以及治疗后第1、3、7和14天，对大鼠进行DW-MRI和[F]FLT PET检查。对肿瘤进行免疫组织化学分析，检测Ki67、TK1和ENT1的表达。

结果

5-FU以剂量依赖的方式抑制CC531肿瘤的生长。免疫组织化学分析未显示Ki67、TK1和ENT1表达有显著变化。然而，用5-FU（60mg/kg）治疗后第4天和第7天，[F]FLT标准化摄取值（SUV）显著升高，并在第14天恢复到基线水平（第-1、4、7和14天的SUV分别为1.1±0.1、2.3±0.5、2.3±0.6和1.5±0.4）。在未治疗的动物中未观察到[F]FLT摄取的变化。此外，与未治疗的大鼠相比，5-FU治疗的大鼠的表观扩散系数（ADC）没有变化。

结论

本研究表明，5-FU治疗可导致肝脏中对治疗有反应的CC531肿瘤的[F]FLT摄取出现短暂升高，而ADC没有显著变化。有必要进行更大规模的未来研究，以进一步调查[F]FLT PET是否能够区分疾病进展和治疗反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16de/5498638/3a45db408012/11307_2016_1021_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16de/5498638/d4dc94e04a44/11307_2016_1021_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/16de/5498638/3a45db408012/11307_2016_1021_Fig7_HTML.jpg

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