^(99)Tc^m-神经紧张肽结肠癌显像的实验研究

Experimental studies of colon carcinoma imaging with ^(99)Tc^m labeled neurotension peptide

目的 探讨99Tcm 神经紧张肽 (NT)显像早期诊断结肠癌的价值。方法 用99Tcm 标记NT进行裸鼠结肠癌模型体内生物分布和显像研究 ,观察受体阻断后99Tcm NT在裸鼠肿瘤模型体内的组织分布和显像特点。测定99Tcm NT与结肠癌细胞的亲和力常数 (Kd)。结果 99Tcm NT对结肠癌细胞Kd为 0 91nmol/L ;标记率 (>94 % )高且稳定。体内生物分布 :99Tcm NT主要经肾脏排泄 ,3和 12h肿瘤 /肌肉比值分别为 3 2 5± 1 0 2和 4 15± 1 4 6 ;受体阻断后 3h肿瘤 /肌肉比值 (1 2 1± 0 6 2 )明显降低 ,与受体未阻断结果相比差异有显著性 (P <0 0 1)。裸鼠肿瘤模型显像时间早 (0 5h开始显影 ) ,3h肿瘤 /对侧肢体比值为 2 6 8± 0 4 4 ;受体阻断后 3h肿瘤 /对侧肢体比值为 1 14± 0 36 ,与受体未阻断结果相比差异有显著性 (P <0 0 1)。结论 99Tcm NT制备方法简单 ,为结肠癌的早期特异性诊断提供了一种可能的新方法。

Objective To prepare neurotension (NT) peptide labeled with 99 Tc m for the early diagnosis of colon carcinoma and to evaluate the advantages of the tracer. Methods Biodistribution studies were performed at 3 and 12 h,respectively after injection of 99 Tc m-NT,and tissue distribution analysis after receptor-blocking was performed at 3 h in nude mice bearing colon carcinoma. Imaging with 99 Tc m-NT was performed at different time points in nude mice bearing colon carcinoma,and imaging after receptor-blocking was also performed at 3 h. The affinity of 99 Tc m-NT binding to the cell of colon carcinoma was studied in vitro. Results The affinity constant of 99 Tc m-NT binding to the cells of colon carcinoma was obtained ( K _d=0.91 nmol/L). The labeling yield of 99 Tc m-NT was more than 94% and the complex was stable in vitro and in vivo. Biodistribution analysis in nude mice bearing colon carcinoma showed that 99 Tc m-NT was excreted chiefly from the kidney,the ratios of tumor to muscle at 3 and 12 h were 3.25±1.02 and 4.15±1.46,respectively. In mice pretreated with unlabeled NT,the uptake of 99 Tc m-NT decreased in the tumor,the ratio of tumor to muscle at 3 h (1.21±0.62) was significantly different from that of the mice without unlabeled NT treatment. Tumor lesion was detected with 99 Tc m-NT earlier (the lesion image showed up at 0.5 h postinjection),the ratio of tumor to contralateral limb at 3 h postinjection was 2.68±0.44 obtained by technique of region of interest (ROI). The ratio at 3 h was 1.14±0.36 and that was significantly different from the ratio at 3 h postinjection in mice pretreated with unlabeled NT. Conclusion The results of all studies in vitro and in vivo indicate that this labeling procedure of 99 Tc m-NT is simple and its specific binding to the cells of colon carcinoma is high,and it is a promising method for diagnosis of colon carcinoma.