荷肝癌小鼠的99Tcm-HL91乏氧显像的实验研究

An experimental study on mice bearing liver cancer imaging with99Tcm-HL91

关键词:  肝癌  小鼠  放射性核素显像  HL91  锝  细胞低氧

Key words:  liver cancer  mice  radionuclide imaging  HL91  technetium  cell hypoxia

摘要:

［目的］探讨⁹⁹Tc^m-HL91（4，9-二氮-3，3，10，10-四甲基十二烷-2，11-二酮二肟）在荷肝癌H22的高淋巴道转移亚系（Hca-F）瘤细胞的BALB/c小鼠中的显像价值。［方法］用1110MBq/2mL的⁹⁹Tc^mO4淋洗液溶解HL91（1 mg），另用10 mL生理盐水溶解1 mg DTPA后，迅速取出50 μL注入上述HL91瓶中，室温下放置10 min后，标记率 ＞95%。13只荷肝癌BALB/c小鼠麻醉后，经尾静脉注射37 MBq ⁹⁹Tc^m-HL91后，2 h 3只、4 h 5只、6 h 5只行SPECT平面显像，利用感兴趣区技术（ROI），分别计算不同时相的靶与非靶T/NT（肿瘤与头部、肿瘤与对侧、肿瘤与腹部）的比值。 ［结果］⁹⁹ Tc^m-HL91在各时相所有荷瘤小鼠的肿瘤均有摄取。注射后4 h放射性最高，随时间推移，6 h略有下降，其放射性下降较其他组织缓慢。HL91在肿瘤乏氧区域高于除腹部外的其他组织。 注射后4 h肿瘤/头部、肿瘤/对侧和肿瘤/腹部的比值分别为4.26±2.29、3.40±0.91和0.41±0.19。肿瘤/头部和肿瘤/对侧比值在4、6 h均高于2 h（P＜0.01）。随时间推移，T/ NT逐渐增高。⁹⁹Tc^m-HL91在肝、肾中滞留最多。 ［结论］ ⁹⁹Tc^m-HL91在荷肝癌BALB/c小鼠的肿瘤中摄取良好、清除缓慢。⁹⁹Tc^m-HL91注射后4 h进行显像可以得到较理想的T/NT比值。乏氧显像中T/NT比值是一个非常重要的指标。

Abstract:

［Objective］To evaluate the value of application on BALB/c mice bearing liver cancer H22 imaging with hypoxia-avid agent⁹⁹Tc^m HL91. ［Methods］ One mg HL91 was dissolved in 2 mL sterile sodium pertechnetate solution containing 1110 MBq(30mCi)⁹⁹Tc^m . A stannous DTPA kit was reconstituted with 10 mL saline, an aliquot of 50 μL was removed and added to the vial containing HL91 and pertechnetate. After 10 minutes at room temperature, the radiochemical purity of the preparation of⁹⁹Tc^m -HL91 was determined before use by paper and thin-layer chromatography, and exceeded 95%. There are 13 BALB/c mice bearing liver cancer HCa-F in the research. After anaesthesia, HL91(37 MBq) was injected intravenously. Three mice were underwent whole body planar static imaging after 2 h injection of⁹⁹Tc^m -HL91, and five mice after 4 h, other five mice after 6h were also performed the same whole body planar imaging. Four regions of interest(ROI) were set on the tumor, head, abdomen and the thorax opposing to the thorax near tumor in the imaging. The radioactivity in the ROIs was measured. The tumor-to-normal tissue ratios of tumor to head, abdomen and thorax were calculated. ［Results］ All of the tumor were found⁹⁹Tc^m -HL91 uptake. The uptake of HL91 in the tumor reached a peak at 4 h and then gradually decreased. After 6h postinjection of⁹⁹Tc^m -HL91, the radioactivity of tumor was descended slightly. HL91 accumulated to highly levels in the hypoxic area than in other tissues except for abdomen. The tumor-to-normal tissue ratios of tumor to head, thorax and abdomen were 4.26±2.29, 3.40±0.91, 0.41±0.19, respectively. The ratio of T/NT at 4 h or 6 h is higher than that of 2 h, there were significant difference (P<0.01). The T/NT continued increase until 6 h postinjection of⁹⁹Tc^m -HL91. However, The radioactivity of abdomen was higher than tumor. ［Conclusions］ High uptake of⁹⁹Tc^m -HL91 in the tumor of BALB/c mice bearing liver cancer H22（H-2）, and the clearance rate is slower. High T/NT can be obtained after 4 h injection of⁹⁹Tc^m -HL91. T/NT is a very important index in tumor hypoxic imaging.