^(99m)TcO(DGDTC)_2肺腺癌Spca-1荷瘤裸鼠实验研究

Biodistribution of ^(99m)TcO(DGDTC)_2 in nude mice bearing Spca-1

目的用99mTcO核标记D-葡萄糖氨基酸盐配合物99mTcO(DGDTC)2观察其在肺腺癌(Spca-1)荷瘤裸鼠体内的摄取情况,并与18F-2-氟-2-脱氧-D-葡萄糖(18F-FDG)的分布情况进行比较,分析99mTcO(DGDTC)2作为肿瘤代谢显像剂的可行性。方法配体交换法制备99mTcO(DGDTC)2,将Spca-1荷瘤裸鼠模型50只分为99mTcO(DGDTC)2组和18F-FDG组,检测血液、肝、肾、肌肉、肿瘤中的单位放射性计数比值(%ID/g)及肿瘤与非肿瘤(T/NT)放射性比值。结果高效液相层析(HPLC)分析法测定99mTcO(DGDTC)2放射性化学纯度≥95%。荷瘤裸鼠体内分布实验结果显示,99mTcO(DGDTC)2组注射显像剂后30 min时血液、肾内%ID/g最高,1 h时显著降低。注射显像剂后30 min、1 h、2 h、3h和4 h时肿瘤组织的%ID/g分别为5.16±0.96、3.18±0.73、1.94±0.39、0.86±0.15和0.34±0.09;T/NT分别为1.7、3.2、3.8、1.9和1.4。18F-FDG组注射显像剂后10 min时血液、肾内%ID/g最高,以后逐渐下降,肿瘤%ID/g最高值出现在10min时。T/NT比值在60 min时达最高值2.5,以后逐渐下降。结论 99mTcO(DGDTC)2放射稳定性较好,荷瘤裸鼠体内分布显示具有较好的肿瘤靶向性,类似于18F-FDG,是一种很有发展前景的肿瘤代谢显像剂。

Objective To observe the biodistribution of 99mTc-labelled deoxyglucose dithiocarbamate compound[99mTcO(DGDTC)2] in the nude mice bearing pulmonary adenocarcinoma cell line Spca-1. Methods 99mTcO(DGDTC)2was prepared using ligand exchange reaction. The radioactive uptake of 99mTcO(DGDTC)2in pulmonary adenocarcinoma cell line Spca-1 and its biodistribution in nude mice with transplanted Spca-1 were measured. A total of 50 nude mice with transplanted Spca-1 were divided equally into 99mTcO(DGDTC)2group(injected99mTcO(DGDTC)23.7 MBq intravenously, and then the mice were killed at 30 min,1 h,2 h,3 h and 4 h, respectively) and18F-FDG group(injected18F-FDG 3.7 MBq intravenously, and then the mice were killed at 10 min, 20 min, 40 min, 60 min and 120 min, respectively). The radioactive distribution(%ID/g) and tumor/non-tumor tissue(T/NT) radioactive ratio in tumor, blood, liver, kidneys and muscles were measured. Results99mTcO(DGDTC)2was successfully prepared and the radiochemical purity(RCP) was ≥95% determinated by high-performance liquid chromatography(HPLC). In99mTcO(DGDTC)2group, the %ID/g in blood and kidneys reached the maximum 30 min after injection, and then gradually decreased. The %ID/g in the tumor at 30 min, 1 h, 2 h, 3 h and 4 h was 5.16±0.96, 3.18±0.73, 1.94±0.39, 0.86±0.15 and 0.34±0.09, respectively. The corresponding T/NT was 1.7, 3.2, 3.8, 1.9 and1.4, respectively. At each time point, the %ID/g in the kidneys was significantly higher than that in the liver, with a peak at 30min, and then decrease after 3 h. In18F-FDG group,the %ID/g in blood and kidneys reached the maximum 10 min after injection, then then gradually decreased. The maximum %ID/g in the tumor was detected at 10 min and the maximum T/NT was detected at 1 h after injection. Both %ID/g and T/NT significantly decreased 2 h after injection. Conclusion The new tracer,99mTcO(DGDTC)2, can be prepared with good quality. The in vivo study demonstrated the high uptake of99mTcO(DGDTC)2in transplanted tumor, implicating the potential application value of99mTcO(DGDTC)2in the diagnostic imaging of lung adenocarcinoma.