乳腺癌BALB/c小鼠生物发光活体成像和小动物~(18)F-FDG PET/CT成像的比较研究
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摘要
目的比较生物发光和小动物PET/CT成像技术在BALB/c小鼠乳腺癌原位移植模型中的显像效果,寻找适合的评价乳腺癌肿瘤模型的分子影像学方法。方法将表达荧光素酶基因的乳腺癌细胞4T1接种于雌性BALB/c小鼠左侧第二对乳房垫下使其成瘤,活体荧光成像和小动物PET/CT成像观察肿瘤的生长情况。~(18)F-FDG PET/CT显像利用IRW软件对图像进行分析,采用感兴趣区技术(ROI)测量组织~(18)F-FDG摄取值。结果生物发光活体成像操作步骤相对较简单;活体荧光成像系统观察能够特异性地探测到肿瘤组织,小动物PET/CT影像观察发现小鼠体内多数器官组织都有~(18)F-FDG摄取,但肿瘤组织在所有组织、器官中~(18)F-FDG摄取值最高;~(18)F-FDG药物吸收时间30~60 min,有放射性,荧光素钾盐药物吸收时间3~5 min,无放射性;小动物PET/CT成像用时20 min,生物发光活体成像用时3 min;小动物PET/CT分辨率<1 mm,生物发光活体成像分辨率1~10 mm;小动物PET/CT呈三维成像,生物发光活体成像呈二维成像。结论生物发光活体成像比~(18)F-FDG PET/CT特异性好,操作简单,图像采集时间短,价钱便宜,无放射性,可检测细胞存活状态,但小动物PET/CT分辨率较高,可精准定位,图像三维立体,可监测到细胞的代谢能力,为以后实验研究中正确选择活体影像学监测手段提供依据。
Objective To compare the effect of bioluminescent imaging and small animal PET/CT imaging technology in breast cancer mouse model, and to find a suitable molecular imaging method for the evaluation of breast cancer model. Methods Luc expressing 4T1 cell was inoculated into the second mammary fat pad on the left side of normal BALB/c mice to establish the tumor models, and then tumor growth was assessed by bioluminescent imaging and small animal PET/CT. PET/CT images were analyzed through IRW(Inveon Research Workplace) to find out region-of-interest. Results The procedure of bioluminescent imaging was relatively simpler than small-animal PET/CT. The tumors could be detected by bioluminescent imaging in a short time, and there was high uptake of ~(18)F-FDG in the tumor with small-animal PET/CT. ~(18)F-FDG absorption time was 30-60 min with radiation, and fluorescein potassium salt absorption time was 3-5 min without radiation. Small-animal PET/CT imaging costed 20 min, but bioluminescent imaging just needed 3 min. Resolution of small-animal PET/CT and bioluminescent imaging was <1 mm and 1-10 mm respectively. PET/CT was a 3D imaging, while the bioluminescent imaging was2D imaging. Conclusions Bioluminescent imaging is better in specificity, simplicity in operation, shorter image acquisition time, cheaper, without radioaction, and can detect cell survival state. Small animal PET/CT has the advantage of high resolution, accurate location, three-dimensional image and cell metabolism monitoring.
Objective To compare the effect of bioluminescent imaging and small animal PET/CT imaging technology in breast cancer mouse model, and to find a suitable molecular imaging method for the evaluation of breast cancer model. Methods Luc expressing 4T1 cell was inoculated into the second mammary fat pad on the left side of normal BALB/c mice to establish the tumor models, and then tumor growth was assessed by bioluminescent imaging and small animal PET/CT. PET/CT images were analyzed through IRW(Inveon Research Workplace) to find out region-of-interest. Results The procedure of bioluminescent imaging was relatively simpler than small-animal PET/CT. The tumors could be detected by bioluminescent imaging in a short time, and there was high uptake of ~(18)F-FDG in the tumor with small-animal PET/CT. ~(18)F-FDG absorption time was 30-60 min with radiation, and fluorescein potassium salt absorption time was 3-5 min without radiation. Small-animal PET/CT imaging costed 20 min, but bioluminescent imaging just needed 3 min. Resolution of small-animal PET/CT and bioluminescent imaging was <1 mm and 1-10 mm respectively. PET/CT was a 3D imaging, while the bioluminescent imaging was2D imaging. Conclusions Bioluminescent imaging is better in specificity, simplicity in operation, shorter image acquisition time, cheaper, without radioaction, and can detect cell survival state. Small animal PET/CT has the advantage of high resolution, accurate location, three-dimensional image and cell metabolism monitoring.
引文
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[13]Sekiguchi Y,Owada J,Oishi H,et al.Noninvasive monitoring ofβ-cell mass and fetalβ-cell genesis in mice using bioluminescence imaging[J].Exp Anim,2012,61(4):445-451.
[14]Kai T,Min F,Joseph A,et al.Imagable 4T1 model for the study of late stage breast cancer[J].BMC Cancer,2008,8:228-247.
[15]李小颖,高凯,董伟,等.荧光素酶标的人肝癌细胞裸鼠异种移植瘤模型的生物发光成像和PET-CT成像比较[J].中国比较医学杂志,2011,21(3):10-13.
[16]胡均松,吴宁,周丽娜,等.小动物PET/CT活体成像时小鼠体温控制系统的设计[J].中国医学影像学杂志,2014,22(6):476-480.
[17]李小颖,马元武,张连峰.三株荧光素酶标记的小鼠乳腺癌细胞在小鼠体内生长及转移的比较[J].中国比较医学杂志,2013,23(4):1-4,79-80.
[18]Deroose CM,De A,Loening AM,et al.Multimodality imaging of tumor xenografts and metastases in mice with combined small animal PET,small-animal CT and bioluminescence imaging[J].J Nucl Med,2007,48(2):295-303.
[19]赵倩,李娟,王荣福.PET/MRI显像技术与其他分子影像技术的比较[J].中国医学装备,2013,10(1):4-7.
[20]何思敏,罗健民,张建平,等.18F-FES小动物PET/CT评价不同乳腺癌模型雌激素受体表达的差异[J].肿瘤影像学,2015,24(1):35-40.
[2]Desantis C E,Fedewa S A,Goding Sauer A,et al.Breast cancer statistics,2015:Convergence of incidence rates between black and white women[J].CA Cancer J Clin,2016,66(1):31-42.
[3]陈万青,张思维,郑荣寿,等.中国2009年恶性肿瘤发病和死亡分析[J].中国肿瘤,2013,22:(1):1-12
[4]李雯雯,赵广银,张兆,等.18F-FDG PET/CT成像观察西妥昔单抗对结直肠癌裸鼠移植肿瘤影响的实验研究[J/CD].中华普通外科学文献(电子版),2015,9(3):188-192.
[5]Salem ML,Shoukry NM,Teleb WK,et al.In vitro and in vivo antitumor effects of the Egyptian scorpion Androctonus amoreuxi venom in an Ehrlich ascites tumor model[J].Springerplus,2016,5:570.
[6]Vantaggiato C,Dell’Omo G,Ramachandran B,et al.Bioluminescence imaging of estrogen receptor activity during breast cancer progression[J].Am J Nucl Med Mol Imaging,2016,6(1):32-41.
[7]Liao D,Luo Y,Markowitz D,et al.Cancer associated fibroblasts promote tumor growth and metastasis by modulating the tumor immune microenvironment in a 4T1 murine breast cancer model[J].PLo S One,2009,4(11):e7965.
[8]Tao K,Fang M,Alroy J,et al.Imagable 4T1 model for the study of late stage breast cancer[J].BMC Cancer,2008,8(228):1-20.
[9]严丽,李莉,郝芳,等.BALB/c小鼠乳腺癌4T1细胞株移植模型的建立[J].中国免疫学杂志,2014,30(6):794-796.
[10]沈国栋,赵婷,张安莉,等.Erb B2高表达的人乳腺癌原位移植瘤裸鼠模型的建立[J].中国药理学通报,2010,26(10):1391-1394.
[11]O'Neill K,Lyons SK,Gallagher WM,et al.Bioluminescent imaging:a critical tool in pre-clinical oncology research[J].J Pathol,2010,220(3):317-327.
[12]Kim JB,Urban K,Cochran E,et al.Non-invasive detection of a small number of bioluminescent cancer cells in vivo[J].Plos One,2010,5(2):e9364
[13]Sekiguchi Y,Owada J,Oishi H,et al.Noninvasive monitoring ofβ-cell mass and fetalβ-cell genesis in mice using bioluminescence imaging[J].Exp Anim,2012,61(4):445-451.
[14]Kai T,Min F,Joseph A,et al.Imagable 4T1 model for the study of late stage breast cancer[J].BMC Cancer,2008,8:228-247.
[15]李小颖,高凯,董伟,等.荧光素酶标的人肝癌细胞裸鼠异种移植瘤模型的生物发光成像和PET-CT成像比较[J].中国比较医学杂志,2011,21(3):10-13.
[16]胡均松,吴宁,周丽娜,等.小动物PET/CT活体成像时小鼠体温控制系统的设计[J].中国医学影像学杂志,2014,22(6):476-480.
[17]李小颖,马元武,张连峰.三株荧光素酶标记的小鼠乳腺癌细胞在小鼠体内生长及转移的比较[J].中国比较医学杂志,2013,23(4):1-4,79-80.
[18]Deroose CM,De A,Loening AM,et al.Multimodality imaging of tumor xenografts and metastases in mice with combined small animal PET,small-animal CT and bioluminescence imaging[J].J Nucl Med,2007,48(2):295-303.
[19]赵倩,李娟,王荣福.PET/MRI显像技术与其他分子影像技术的比较[J].中国医学装备,2013,10(1):4-7.
[20]何思敏,罗健民,张建平,等.18F-FES小动物PET/CT评价不同乳腺癌模型雌激素受体表达的差异[J].肿瘤影像学,2015,24(1):35-40.