18F-NaF PET-CT显像技术辅助下的前列腺癌骨转移动物模型建立

尤强; 蔡华伟; 庞富文等

18F-NaF PET-CT显像技术辅助下的前列腺癌骨转移动物模型建立

Establishment of Bone Metastasis Model of Prostate Cancer in Mice with Monitoring of 18F-NaF PET-CT

摘要

摘要: 【摘要】目的胫骨骨髓腔注射法建立前列腺癌PC3骨转移动物模型，采用¹⁸F-NaF 正电子发射计算机断层显像（PET-CT）核医学影像与X射线平片、显微CT影像等方式监测并比较肿瘤在骨组织的局部生长及其对骨组织的破坏情况。方法肿瘤10只6周龄Balb/c雄性裸鼠麻醉后，从左侧胫骨近端关节面将PC3细胞悬液2 μL（2×105细胞）注入胫骨骨髓腔，建立骨转移模型；对照组6只裸鼠从相同位置注入等体积生理盐水。持续记录观察裸鼠的活动及体质量。术前、术后检测血清碱性磷酸酶（ALP）。21 d后，裸鼠进行X射线、显微CT及¹⁸F-NaF PET-CT检查，观察骨破坏情况。检查完毕后处死裸鼠，取骨组织石蜡包埋切片后经苏木素伊红（HE）染色，在显微镜下观察组织学情况。结果截止实验结束时，10只裸鼠骨转移模型全部成功。肿瘤细胞接种后21 d，单纯X射线检查或显微CT无法确诊肿瘤组是否存在骨皮质破坏，但同期¹⁸F-NaF PET-CT检查可见肿瘤组胫骨髓腔内出现明显放射性信号，感兴趣区域（ROI）平均标准摄取值最大值SUVmax值为2.10±0.13，高于对照组（0.62±0.14），两者相比差异有统计学意义（P <0.05），提示有肿瘤造成的骨质代谢异常。术后3周肿瘤组血清ALP为（207.87±44.18） U/L，远高于对照组〔（82.75±17.27） U/L〕（P <0.05）。组织病理学检测结果证实肿瘤组胫骨髓腔内出现异常骨质增生。结论利用¹⁸F-NaF PET-CT影像监测成功建立了前列腺癌PC-3的早期骨转移动物模型，模拟了前列腺癌对骨组织的成骨侵袭和破坏行为，为进一步研究前列腺癌的早期骨转移机制奠定了基础。

Abstract: 【Abstract】 Objective To establish a mouse model bearing human prostate cancer xenograft with bone metastasis by the monitoring with X-Ray, Micro CT, and _{18F-NaF PET/CT. Methods Sixteen male Balb/c nude mice were allocated into control (6 mice) and experimental group (10 mice). In experimental group, the mice were subjected to percutaneous injection of 2×10⁵PC-3 cells into tibial plateau, bone defects were assessed after 21 d by X-ray, Micro-CT and ¹⁸F-NaF PET/CT, and bone damages were evaluated by HE staining. In control group, equal volume of saline was injected into the mice. Results At 21 d post modeling, the significant radioactive ¹⁸F-NaF signals were found in the tibial intramedullary cavity of all 10 mice in experimental group. The ROI value evaluation showed that SUV_maxin control group was 0.62±0.14, but SUV_maxin tumor group was 2.10±0.13，which indicated abnormal bone metabolism. The serum alkaline phosphate level and HE staining results also confirmed that tumor mediated bone destruction and osteogenesis. However, X-ray and Micro-CT did not indicate precise diagnostic bone defect. Conclusion Bone metastasis model of prostate PC-3 cancer cells were successfully established by intratibial injection. ¹⁸F-NaF PET/CT could detect tumor invasion and bone osteogenesis in the early stage of modeling.}

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