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氟脱氧葡萄糖和氟代胸苷 PET/CT 成像在结直肠癌异种移植模型中评估伊立替康治疗的药效学。

Pharmacodynamic evaluation of irinotecan therapy by FDG and FLT PET/CT imaging in a colorectal cancer xenograft model.

机构信息

Translational Imaging and Biochemical Biomarkers, Advanced Technology, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, USA.

出版信息

Mol Imaging Biol. 2012 Oct;14(5):617-24. doi: 10.1007/s11307-011-0529-8.

DOI:10.1007/s11307-011-0529-8
PMID:22167582
Abstract

PURPOSE

Longitudinal changes of 3'-[(18) F]fluoro-3'-deoxythymidine (FLT) and 2-deoxy-2-[(18) F]fluoro-D-glucose (FDG) in response to irinotecan therapy in an animal model of colorectal cancer were compared.

PROCEDURES

SCID/CB-17 mice with HCT116 tumors were treated with 50 mg/kg irinotecan by intraperitoneal injection weekly for 3 weeks. FLT and FDG-positron emission tomography (PET) were performed at baseline, the day after each treatment, and 5 days after the first treatment. Proliferation and apoptosis were evaluated by immunohistochemistry (IHC) after day 15 of imaging.

RESULTS

Irinotecan treatment resulted in a suppression of tumor growth. Tumor FLT uptake was decreased the day after each treatment but to a lesser extent 5 days after the first treatment. FDG uptake increased the day after each treatment with a continuous increase throughout the experiment. IHC analysis of phospho-H3 and Ki67 confirmed FLT-PET results, indicating a decrease in proliferation the day after the final irinotecan treatment. Increased apoptosis monitored by caspase-3 was observed after day 15 with irinotecan treatment.

CONCLUSIONS

FLT-PET may be a better method than FDG-PET for assessing treatment response to irinotecan. Changes in imaging occur before changes in tumor volume.

摘要

目的

比较氟代胸苷(FLT)和 2-脱氧-2-氟代-D-葡萄糖(FDG)在结直肠癌动物模型中对伊立替康治疗的纵向变化。

方法

SCID/CB-17 荷 HCT116 肿瘤小鼠每周腹腔注射 50mg/kg 伊立替康 3 周。在基线、每次治疗后第 1 天和第 1 次治疗后 5 天进行 FLT 和 FDG 正电子发射断层扫描(PET)。在成像后第 15 天通过免疫组化(IHC)评估增殖和凋亡。

结果

伊立替康治疗导致肿瘤生长受到抑制。肿瘤 FLT 摄取在每次治疗后第 1 天减少,但在第 1 次治疗后第 5 天减少较少。FDG 摄取在每次治疗后第 1 天增加,整个实验过程中持续增加。磷酸化 H3 和 Ki67 的 IHC 分析证实了 FLT-PET 结果,表明最后一次伊立替康治疗后第 1 天增殖减少。伊立替康治疗后第 15 天观察到 caspase-3 监测的凋亡增加。

结论

FLT-PET 可能是评估伊立替康治疗反应的比 FDG-PET 更好的方法。成像变化发生在肿瘤体积变化之前。

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