PET/CT对小动物前列腺癌骨转移的观察研究
|
摘要
目的探讨小动物PET/CT扫描在小鼠前列腺癌骨转移检测中的可行性。方法裸鼠23只,随机分为对照组2只,前列腺原位注射组、左心室注射组、胫骨腔内注射组每组各7只。分别采用前列腺原位注射、左心室内注射、胫骨腔内注射的方法建立前列腺癌骨转移动物模型。建模成功后饲养40天,原位注射及左心室注射组采用PET/CT扫描检测,胫骨腔注射组采用小动物高分辨率CT检测,对可疑的骨转移灶行解剖学观察及HE染色明确。结果前列腺原位注射组肿瘤细胞聚集腹腔软组织内生长,均未发现明显骨质破坏(0/7);左心室注射组均发生皮下等软组织转移(7/7),PET/CT检测出一例胫骨上端骨质破坏,组织学检测证实为骨转移灶(1/7);胫骨腔注射组所有动物均形成明显骨质破坏(7/7)且高分辨率CT检测见骨破坏分级良好。结论小动物PET/CT扫描能够良好的显示转移灶在小鼠体内的定位,且能良好的显示骨破坏情况,因此该技术在检测小动物骨转移上有着良好的可行性。
Objective To investigate the viability of small animal micro-PET/CT scan for detection of prostate cancer bone metastasis in nude mouse prostate cancer bone metastasis models. Methods 23 nude mice were divided into control group(2 mice),orthotopic injection group(7 mice),intracardiac injection group(7 mice),intratibial injection group(7 mice), randomly. 40 days after the tumor cells injection, the animal were taken for PET/CT scanning(orthotopic injection group &intratibial injection group) and high-resolution micro-CT scanning(intratibial injection group). After the examination, the animals were sacrificed and dissected to identify metastasis tumor tissue. Suspicious bone metastasis was fixed in 10% formalin for histological examination. Results In the orthotopic injection group, no obvious bone destruction was detected(0/7). In the intracardiac injection model, one upper tibia bone destruction was detected by PET/CT scanning, which was confirmed by the high-resolution micro-CT scanning and HE stain; In the intratibial injection model, all animals formed various degrees of bone destruction(7/7) and the high-resolution micro-CT scanning showed various degrees of bone destruction clearly. Conclusion PET/CT scanning can identify the location of bone metastasis and the degrees of bone destruction clearly, which can serve as a promising method for cancer bone metastasis research.
Objective To investigate the viability of small animal micro-PET/CT scan for detection of prostate cancer bone metastasis in nude mouse prostate cancer bone metastasis models. Methods 23 nude mice were divided into control group(2 mice),orthotopic injection group(7 mice),intracardiac injection group(7 mice),intratibial injection group(7 mice), randomly. 40 days after the tumor cells injection, the animal were taken for PET/CT scanning(orthotopic injection group &intratibial injection group) and high-resolution micro-CT scanning(intratibial injection group). After the examination, the animals were sacrificed and dissected to identify metastasis tumor tissue. Suspicious bone metastasis was fixed in 10% formalin for histological examination. Results In the orthotopic injection group, no obvious bone destruction was detected(0/7). In the intracardiac injection model, one upper tibia bone destruction was detected by PET/CT scanning, which was confirmed by the high-resolution micro-CT scanning and HE stain; In the intratibial injection model, all animals formed various degrees of bone destruction(7/7) and the high-resolution micro-CT scanning showed various degrees of bone destruction clearly. Conclusion PET/CT scanning can identify the location of bone metastasis and the degrees of bone destruction clearly, which can serve as a promising method for cancer bone metastasis research.
引文
[1]毕新刚,韩仁强,周金意.2009年中国前列腺癌发病和死亡分析[J].中国肿瘤,2013,22(6):417-422.
[2]Singh AS,Figg WD.In vivo models of prostate cancer metastasis to bone[J].J Urol,2005,174(3):820-826.
[3]Wan X,Li ZG,Yingling JM,et al.Effect of transforming growth factor beta(TGF-β)receptor I kinase inhibitor on prostate cancer bone growth[J].bone,2012,50(3):695-703.
[4]Yang M,Jiang P,Sun FX.A fluorescent orthotopic bone metastasis model of human prostate cancer[J].Cancer Research,1999,59(4):781-786.
[5]Corey E,Quinn JE,Vessella RL.A novel method of generating prostate cancer metastases from orthotopic implants[J].Prostate,2003,56(2):110-114.
[6]孙萍,王怡,孙志东,等.利用荧光素酶标记的肿瘤细胞建立肝原位移植模型及其活体成像[J].生物技术通讯,2008,19(3):383-385.
[7]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.
[8]Wang H,Yu C,Gao X,et al.The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells[J].Cancer Cell,2015,27(2):193-210.
[9]李天然,田嘉禾.小动物PET及PET-CT及其在分子影像学中的应用[J].国际放射医学核医学杂志,2008,32(1):1-4.
[10]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.
[11]Valastyan S,Weinberg RA.Tumor metastasis:molecular insights and evolving paradigms[J].Cell,2011,147(2):275-292.
[12]Cox TR,Rumney RM,Schoof EM,et al.The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase[J].Nature,2015,522(7554):106-110.
[13]Fernandes RS,Dos Santos Ferreira D,de Aguiar Ferreira C,et al.Development of imaging probes for bone cancer in animal models.Asystematic review[J].Biomed Pharmacother,2016,83:1253-1264.
[2]Singh AS,Figg WD.In vivo models of prostate cancer metastasis to bone[J].J Urol,2005,174(3):820-826.
[3]Wan X,Li ZG,Yingling JM,et al.Effect of transforming growth factor beta(TGF-β)receptor I kinase inhibitor on prostate cancer bone growth[J].bone,2012,50(3):695-703.
[4]Yang M,Jiang P,Sun FX.A fluorescent orthotopic bone metastasis model of human prostate cancer[J].Cancer Research,1999,59(4):781-786.
[5]Corey E,Quinn JE,Vessella RL.A novel method of generating prostate cancer metastases from orthotopic implants[J].Prostate,2003,56(2):110-114.
[6]孙萍,王怡,孙志东,等.利用荧光素酶标记的肿瘤细胞建立肝原位移植模型及其活体成像[J].生物技术通讯,2008,19(3):383-385.
[7]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.
[8]Wang H,Yu C,Gao X,et al.The osteogenic niche promotes early-stage bone colonization of disseminated breast cancer cells[J].Cancer Cell,2015,27(2):193-210.
[9]李天然,田嘉禾.小动物PET及PET-CT及其在分子影像学中的应用[J].国际放射医学核医学杂志,2008,32(1):1-4.
[10]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.
[11]Valastyan S,Weinberg RA.Tumor metastasis:molecular insights and evolving paradigms[J].Cell,2011,147(2):275-292.
[12]Cox TR,Rumney RM,Schoof EM,et al.The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase[J].Nature,2015,522(7554):106-110.
[13]Fernandes RS,Dos Santos Ferreira D,de Aguiar Ferreira C,et al.Development of imaging probes for bone cancer in animal models.Asystematic review[J].Biomed Pharmacother,2016,83:1253-1264.