99Tcm-EGF的直接法合成及其在荷C6动物体内生物学分布

探索用⁹⁹Tc^m直接标记表皮生长因子（EGF）的方法并研究其在荷C6动物体内的生物学分布特点。巯基乙醇（20 mL/L）10 μL还原EGF（2.5 μg）；含0.5 μg SnCl2的亚甲基二膦酸盐（MDP）溶液将还原高价锝使之与还原EGF的巯基结合，放化纯度大于95%，标记物稳定性较好，在6 h内放化纯度大于95%。通过内皮细胞培养进行⁹⁹Tc^m-EGF的生物活性鉴定，显示EGF在锝标记前后生物学活性未见明显改变（P＞0.05）。⁹⁹Tc^m -EGF在荷瘤鼠体内生物学分布显示肝、脾、肾等组织放射性分布较高，瘤区放射性较高，而脑组织最低，4 h瘤与正常组织放射性摄取比值(Tumor/Normal Tissue)为2.25， SPECT全身显像显示瘤组织放射性核素浓聚。因此直接合成的⁹⁹Tc^m-EGF可望成为特异性诊断高表达EGFR肿瘤的SPECT分子显像剂。

Direct Radiolabeled 99Tcm-EGF and Biological Distribution in C6 Rats

The method of technetium-99m direct radiolabeling of epidermal growth factor (EGF) and the biological distribution characteristics of ⁹⁹Tc^m EGF in C6 bearing rats were explored. Following reduction of EGF（2.5 μg） with 2 ME（20 mL/L， 10 μL）， EGF was labeled with ⁹⁹Tc^m in the presence of SnCl₂（0.5 μg）. The results show that radiochemical purity of ⁹⁹Tc^m-EGF is more than 95% and ⁹⁹Tc^m-EGF is of the characteristic of stability. The biological activity analyzed by the culture of endothelial cells shows that there is no significant difference between ⁹⁹Tc^m-EGF and EGF（P＞0.05）. Biological distribution is observed at different time point after injection of ⁹⁹Tc^m EGF into tumor bearing Wistar rats, and shows ⁹⁹Tc^m EGF is mainly accumulated in liver, kidney and spleen and least accumulated in the brain. Tumor take relatively high concentration of ⁹⁹Tc^m EGF and the uptake ratio of tumor to normal tissue is 2.25 at 4 h. So ⁹⁹Tc^m EGF prepared by this direct method appears to be a feasible way to detect the tumors expressing high EGFR（such as glioma）.