99Tcm-HL91和18F-FDG显像与放疗关系的实验研究

Experimental study on the relationship between radiotherapy effect and 99Tcm-HL91 and 18F-FDG imaging

    摘要
  • 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18FFDG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，4 h后分别于放疗前、放疗后1 h、2 d和10 d进行显像。④18F-FDG显像：分别于放疗前和放疗后11 d进行18F-FDG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。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1 h、2 d、10 d99Tcm-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2 d时段出现加重。②放疗前和放疗后11 d18F-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99Tcm-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。

     

    Abstract:
    Objective To investigate the relationship between radiotherapy effect and 99Tcm-4, 9-diaza-2, 3, 10, 10-tetramethyldodecan-2, 11-dioxime(99Tcm-HL91)and18F-FDG imaging in S180 mouse.
    Methods ①Animals: 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 of 2×106cells.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 MBq99Tcm-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 18FFDG 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.

     

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