HSV1-tk乳腺癌移植瘤裸鼠模型PET-CT报告基因显像  

Molecular imaging for PET-CT reporter gene in breast adenocarcinoma （HSVI-tk） of subcutaneous xenografts in living nude mice

作　　者：徐文贵[1] 戴东[1] 房娜 宋秀宇[1] 王健[1] 朱研佳[1] 门晓媛[1] 

机构地区：[1]乳腺癌防治教育部重点实验室、天津市“肿瘤防治”重点实验室、天津医科大学附属肿瘤医院中国科学院高能物理所“肿瘤分子影像联合实验室”、天津医科大学附属肿瘤医院分子影像及核医学诊疗科,天津300060 [2]青岛市中心医院PET-CT中心

出　　处：《中华医学杂志》2009年第48期3420-3424,共5页National Medical Journal of China

基　　金：国家自然科学基金（30872954）;天津市自然科学基金（08JCZDJC23700）;天津市科委面上项目（07JCYBJC09300）

摘　　要：目的对^18F-FHBG体外摄取、体内分布及荷瘤裸鼠PET—CT显像等方面进行研究。方法利用吖井型计数器测定体外肿瘤细胞T47D和T47D—tk对^18F-FHBG的摄取、正常昆明小鼠和移植瘤裸鼠^18F-FHBG体内分布；并进行荷皮下移植瘤裸鼠^18F-FHBGPET-CT显像。结果体外肿瘤细胞摄取实验显示T47D-tk细胞摄取^18F-FHBG的程度明显高于正常的T47D细胞，120min时T47D—tk细胞对^18F-FHBG的摄取为T47D细胞的64倍（P〈0．001）。正常小鼠注射^18F-FHBG后，主要分布于肝脏、肠道、肾脏和膀胱，而脑部未见明显放射性分布。荷皮下移植瘤裸鼠PET—CT显像显示，T47D．tk肿瘤浓聚^18F-FHBG的程度明显高于T47D肿瘤，且2h显像效果较好。结论体外T47D—tk细胞摄取^18F-FHBG的程度明显高于正常的T47D细胞；在小鼠体内^18F-FHBG主要经肠道和泌尿系统排泄。^18F-FHBG报告基因探针可以有效的定位于HSV1-tk基因表达的部位且与移植瘤裸鼠体内分布研究结果一致。这可为进一步开展^18F-FHBG报告基因显像与肿瘤基因治疗的监测提供有效手段和科学依据。Objective To study the in vitro accumulation of JSF-FHBG, its in vivo distribution and ^18F-FHBG PET-CT imaging for reporter gene （HSVI-tk） in nude mice with a xenograft of breast adenocarcinoma. Methods The in vitro uptake of ISF-FHBG in tumor cells of T47D and T47D-tk and the distribution of^18F-FHBG in normal Kunming mice and nude ）nice with breast adenocarcinoma xenograft were detected by well-type γ counter. Reporter gene PET-CT imaging with ^18F-FHBG was performed in nude mice with a xenograft of breast adenocarcinoma. And the expression location of HSVI-tk gene could be monitored by observing the in vitro and in vivo accumulation of ^18F-FHBG. Results The in vitro uptake of ^18F-FHBG in T47D-tk cells （ 143.67 dpm/104 ＋ 5.82 dpm/lO4 cells） was significantly higher than that in T47D cells （2. 23 dpm/104 ＋ 0. 23 dpm/104 cells） at 60 and 120 rain post-injection （P 〈 0. 001 ） and reaches a plateau at 60 min. In normal Kunming mice, ^18F-FHBG was mainly distributed in liver, intestine, kidney and bladder while there was no obvious radioactive accumulation in brain, ^18F--FHBG accumulated at a significantly higher level in T47D-tk tumors than in T47D tumors and its accumulation yielded the best image effect at 2 h by PET-CT imaging in nude mice. Conclusion The in vitro uptake of ^18F-FHBG in T47D-tk cells is significantly higher than that in T47D cells. ^18F-FHBG is mainly excreted by digestive tract and urinary tract in mice. It agrees with the expression pattern of HSVl-tk gene. ^18F-FHBG can determine the localization of HSVI-tk gene expression in an efficient way. This study will offer a monitoring method and scientific base for is F-FHBG reporter gene imaging and HSV1-tk gene therapy in tumors.

关 键 词：基因探针 ^18F-FHBG PET—CT显像 HSV1-tk基因 乳腺癌 

分 类 号：R737.9[医药卫生—肿瘤]