肿瘤表皮生长因子受体的分子显像研究

Molecular imaging of epidermal growth factor receptor in glioma-bearing rats

目的探讨^11C标记的喹唑林小分子PD153035在肿瘤表皮生长因子受体（EGFR）显像中的价值。方法建立大鼠皮下神经胶质瘤模型，经尾静脉注射^11C-PD153035（15—20MBq／0．3ml），即刻进行PET-CT扫描，并连续采集图像。利用感兴趣区技术检测^11C-PD153035在荷瘤鼠体内重要组织器官的放射性分布以及被肿瘤组织的摄取情况。通过体外阻断实验观察PD153035对C6细胞摄取^11C-PD153035的阻断作用。结果^11C-PD153035在大鼠各重要脏器内分布的强度和达到高峰的时问均不同，由强到弱分别为肝脏、消化道、肾脏和心脏，而在肺、肌肉及脑中的分布较低。^11C-PD153035在肿瘤中也有一定程度的摄取，而且肿瘤组织摄取放射活性的最高值是正常组织的4．15倍。体外实验证明，C6细胞对^11C-PD153035的摄取可被PD153035阻断。结论^11C-PD153035在大鼠体内可被肿瘤摄取，有可能成为肿瘤EGFR的PET显像剂，但^11C-PD153035在胃肠道的高浓度分布将影响其在该区域肿瘤显像中的应用。

Objective To investigate the value of UC-PD153035 as an EGFR imaging agent in C6 tumor-bearing rat. Methods The tumor-bearing rats were generated by subcutaneous injection of glioma C6 cells. Positron emission tomography/computer tomography （PET/CT） scans started as soon as intravenous injection of 11C-PD153035 （15-20 MBq/0.3 ml） was completed, images were collected continuously. The region of interest （ROI） was used to study the percentage of radioactivity in major organs and implanted tumors in the rats. The accumulation and blocking study in vitro was completed. Results There were significant differences in U C-PD153035 uptake among major organs. The maximum uptake in the organs ranked in the following order： liver 〉 gastrointestinal tract 〉 kidney 〉 lung 〉 brain 〉 muscle. Radioactivity could be also observed in the tumors. The radioactivity ratio （T/NT, target/non-target） peaked （4.15） at 40 - 50 min post injection. The in vitro blocking study showed that u C-PD153035 uptaken by C6 cells could be blocked by PD153035. Conclusion The results of this study show that 11C-PD153035 can be uptaken by EGFR-expressing tumors, n C-PD153035 has a potential as a bioprobe to yield useful information for beth diagnosis and therapy of tumors. However, the high concentration of 11 C-PD153035 in the gastrointestinal tract is unfavorably affecting the tumor detection in these organs.