摘要目的 用99Tcm-4,9-二氮-2,3,10,10-四甲基十二烷-2,11-二酮肟(99Tcm-HL91)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:选取20只昆明种、清洁级健康成年雄性小鼠供实验用(另备5只用于腹水模型),采用完全随机方法分为2组(对照组和实验组),每组10只.②细胞:将S180腹水瘤细胞株复苏后分别接种于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.③99Tcm-HL91显像:通过小鼠尾静脉注射99Tcm-HL91 37 MBq,4h后分别于放疗前、放疗后1h、2d和10d进行最像.④18F-FDG显像:分别于放疗前和放疗后11d进行18F-FDG显像.显像前12 h禁食,小鼠尾静脉注射18F-FDG 11.5MBq,30 min后腹腔注射0.1％戊巴比妥钠麻醉.⑤放射治疗:第1次99Tcm-HL91和18F-FDG显像结束后,2组小鼠分别给予0 Gy和8 Gy的X线照射.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1h、2d、10d 99Tcm-HL91的UR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无明显递减趋势,表明肿瘤乏氧状态未见减低,甚至在2d时段出现加重.②放疗前和放疗后11 d 18F-FDG显像的UR分别为2.49±1.29和1.49±0.56,UR亦呈现依次递减趋势,与99Tcm-HL91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分别为2.22±0.45和1.89±0.08,UR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99cm-HL91显像的UR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.

abstractsObjective To investigate the relationship between radiotherapy effect and 99Tcm-4,9-diaza-2,3,10,10-tetramethyldodecan-2,11-dioxime (99Tcm-HL91) and 18F -FDG imaging in S180 mouse.Methods ① Animals:twenty male Kunming mice were randomly divided into two groups of radiotherapy and non-radiotherapy control group.②Cells:S180 cell lines were injected into peritoneal cavity of the other 5 mice.When the S180 tumor developed,1ml liquid were dripped and diluted to the suspension solution of2×106cells.Then,0.2 ml cells solution were was injected into the hippo of right rear leg of mice.The mouse model was used to experiment while the tumor dimension developed to 1-1.5 cm.③99Tcm-HL91 imaging:37 MBq 99Tcm-HL91 was injected into mouse models by tail vein.After 4 h,SPECT were performed before and at 1 h,2 d and 10 d after radiotherapy.④18F-FDG imaging:11.5 MBq 18F-FDG was injected into mouse models by tail vein.After 30 min,SPECT were perfored before and after radiotherapy at the time of 11 d.⑤Radiotherapy:two groups of mice were irradiated to 0 Gy and 8 Gy X-ray after the first 99Tcm-HL91 and 18F-FDG imaging.⑥Images analysis:the region of interest(ROI) region,in tumor and lung site,was drawed to calculate the uptake ratio(UR).Results Before and at 1 h,2 d,and 10 d after radiotherapy,the UR in 99Tcm-HL91 imaging were 3.53±1.62,3.41± 1.42,2.55± 1.57 and 1.26±0.03,respectively,while the UR 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 developed reoxygenation.Before and at 11d after radiotherapy,the UR in 18F-FDG imaging were 2.49±1.29 and 1.49±0.56,while the UR were 2.22±0.45 and 1.89±0.08 in control group,which suggested a coincident trend with 99Tcm-HL91 imaging.The tumor glucose metabolism rate was also decreased which suggested a good radiotherapy outcome.Conclusions 99Tcm-HL91 UR can effectively be used to evaluate the tumor hypoxic level in vivo.This affords a new useful method to assess the whole volume of tumor hypoxic level in clinic.