【作者】 杨爱民； 于燕； 邓惠兴； 李洁； 李旭； 陈葳； 罗伟；

【Author】 Yang Ai-min,Yu Yan,Deng Hui-xing,Li Jie,Li Xu,Chen Wei,Luo Wei (1.Department of nuclear medicine,the first hospital,medical school of Xi’an Jiaotong university;2.Hygine faculty,medical school of Xi’an Jiaotong university;3.Molecular and biology center,the first hospital,medical school of Xi’an Jiaotong university;4.Radiotherapy center,the first hospital,medical school of Xi’an Jiaotong university.)

【机构】 西安交通大学医学院第一附属医院核医学科； 西安交通大学医学院卫生系； 西安交通大学医学院第一附属医院分子生物学中心； 西安交通大学医学院第一附属医院放射治疗中心；

【摘要】 目的:用⁹⁹Tc^m-HL-91和18F-FDG为显像剂,探讨肿瘤放疗前、后的乏氧状态与放疗疗效之间的关系。方法:（1）动物:昆明种、清洁级健康成年雄性小鼠由西安交通大学医学院实验动物中心提供并饲养,选取20只小鼠供实验用,体质量（27±3）g,采用完全随机方法分为2组（对照组和实验组）。（2）细胞:S180腹水瘤细胞株由西安交通大学医学院第一附属医院分子生物中心提供,复苏后分别接种于5只小鼠腹腔,待腹水形成后,抽取1 ml稀释至活瘤细胞计数大于2×10⁶个/ml瘤细胞悬液,于每只小鼠右后肢皮下接种0.2 ml。待瘤体长至1～1.5 cm时用于实验。（3）⁹⁹Tc^m-HL-91显像:⁹⁹Tc^m-HL-91由广东希埃核医药中心提供,通过小鼠尾静脉注射⁹⁹T^m-HL-91 37 MBq 4 h后,分别于放疗前、放疗后1 h、2 d和10 d进行显像。。仪器采用美国GE Hawkeye VG SPECT仪,配以低能通用准直器,矩阵128×128,采集时间150 s,放大倍数1.3。（4）18F-FDG显像:18F-FDG由广东希埃核医药中心提供,分别于放疗前和放疗后11 d进行显像。显像前12 h禁食,小鼠尾静脉注射¹⁸F-FDG 11.5 MBq 30 min后腹腔注射0.1%戊巴比妥钠麻醉,采用美国GE Hawkeye VG SPECT仪,配以高能符合线路准直器,矩阵128×128,采集时间150 s,放大倍数1.3。（5）放射治疗:第1次⁹⁹Tc^m-HL-91和¹⁸F-FDG显像结束后,2组小鼠分别给予0和8 Gy的X线加速器照射。（6）图像处理和半定量分析:于图像上肿瘤部位和小鼠肺野设等大感兴趣区（ROI）,获得显像中瘤/非瘤（T/NT）摄取比值（UR）。结果:（1）放疗前和放疗后1 h、2 d、10d HL-91的UR值分别为3.53±1.62、3.41±1.42、2.55±1.57和1.26±0.03,表明放疗后肿瘤出现再氧合,乏氧状态依次减低。对照组各时相的UR值分别为3.62±1.65、3.02±1.94、4.10±1.48和2.96±2.02,UR值无明显递减趋势,表明肿瘤乏氧状态未见减低,甚至在2 d时段出现加重。（2）放疗前和放疗后11d¹⁸F-FDG显像的UR比值分别为2.49±1.29和1.49±0.56,UR值亦呈现依次递减趋势,与HL-91显像一致。表明放疗后肿瘤葡萄糖代谢活性减低。对照组的UR值分别为2.22±0.45和1.89±0.08,UR值也出现减低,但变化不明显,而且大部分小鼠在显像前死亡。结论:放疗前后⁹⁹Tc^m-HL-91显像的UR比值能够较好地评价肿瘤乏氧水平,并可初步评价疗效,为在活体评价放疗后肿瘤再氧合过程提供了一种新方法。更多还原

【Abstract】 To investigate the relationship between radiotherapy effect and ⁹⁹Tc^m - HL-91 and ¹⁸F-FDG imaging in S180 mouse.Methods:Animal:twenty male Kunming mice（27±3g）,obtained from animal center of medical school of Xi’an Jiaotong university,were randomly divided into two groups of radiotherapy and non-radiotherapy control group.Cells:S180 cell lines,obtained from molecular and biology center of medical school of Xi’an Jiaotong university,were thawed injected into peritoneal cavity of the 5 mouse.When the S180 tumor liquid developed,1ml liquid were dripped and dilute to the suspension solution of 2×106 cells.Then,0.2ml of it was injected into the hippo of right rear leg of mouse.The mouse model was used to experiment while the tumor dimension developed to 1-1.5 cm.⁹⁹Tc^m -HL-91 imaging:37 MBq ⁹⁹Tc^m -HL-91, obtained from Guangdong xiai radio-pharmaceutical center,was injected into mouse models by tail vein.After for 4h, SPECT imaging were taken before and after radiotherapy at the time of 1h、2d and 10d.GE Hawkeye VG SPECT,equipped with low energy collimator,matrix 128×128,zoom 1.3,was used to acquisite images for 150 seconds.Radiotherapy:Two groups mouse was irradiated to 0Gy and 8Gy X-ray after the first ⁹⁹Tc^m -HL-91and ¹⁸F-FDG imaging.Images analysis:the ROI region,in tumor and lung site,was drawed for calculate the UR（uptake ratio）.Results:,After 1 h、2d and 10d of radiation exposure,the UR values in ⁹⁹Tc^m -HL-91 imaging were 3.53±1.62、3.41±1.42、2.55±1.57 and 1.26±0.03, respectively,while the UR values were 3.62±1.65、3.02±1.94、4.10±1.48 and 2.96±2.02 in control group.This revealed that tumors hypoxic level was decreased after radiation and suggested that tumors develop re-oxygenation.After 11d of radiation exposure,the UR values in ¹⁸F-FDG imaging were 2.49±1.29 and 1.49±0.56,while the UR values were 2.22±0.45 and 1.89±0.08,expressing a coincident trend with ⁹⁹Tc^m-HL-91 imaging.This hint that the tumor metabolic sate was also decreased suggesting a good radiotherapy outcome.Conclusion:⁹⁹Tc^m c -HL-91 UR value can effectively evaluate the tumor hypoxic level in vivo.This affords a new useful method to access the whole volume of tumor hypoxic level in clinic.更多还原