188Re-胰岛素样生长因子1类似物在荷人胰腺癌裸鼠体内分布及其显像研究

Studies on biodistribution and imaging of 188Re labeled insulin-like growth factor-1 analogue in nude mice bearing human pancreatic carcinoma

目的研究188Re标记胰岛素样生长因子1类似物（IGF-1A）在荷人胰腺癌裸鼠体内的分布及其显像。方法①直接法标记188Re—IGF-1A并测定标记率。②建立荷人胰腺癌Patu8988裸鼠模型。③188Re—IGF-1A经瘤内注射荷人胰腺癌裸鼠瘤内，分别于注射后15min、1h、4h、24h、3d、5d进行SPECT平面显像。④188ReO4-经瘤内注射后15min、1h、2h、4h、24h进行显像，取各时间组裸鼠（n=4）脏器和肿瘤组织，计算每克组织百分注入剂量（％ID／g）及肿瘤月乍肿瘤组织放射性摄取比值（T／NT）。结果①188Re—IGF-1A标记率为（94．07±0．32）％。②瘤内注射188Re—IGF-1A后，肿瘤部位放射性积聚量4h内差异无统计学意义（F=1．622，P〉0．05），且随时间延长，肿瘤与其他脏器的T/NT呈上升趋势，其中肿瘤，肌肉在5d时最高，达到6531．79±4930．26。③瘤内注射188ReO4-后，在体内初始主要分布于甲状腺、胃、肿瘤、血液，随时间延长，肿瘤部位放射性计数迅速下降。④在24h，瘤内注射188Re—IGF-1A组肿瘤及肾脏内％ID／g较188ReO4-组高，两者有统计学差异（t=5．877，t=13．287，P〈0．01）；两组肿瘤内％ID／g比值在24h达到最高，为74．10倍。⑤瘤内注射188Re—IGF-1A后，SPECT平面显像见瘤内浓聚，5d时仅见肿瘤部位显影。结论188Re—IGF-1A对胰腺癌具有良好的亲和力，在肿瘤部位有较高的T/NT，可望作为胰腺癌治疗的药物。

Objective To evaluate the biodistribution and planar gamma camera imaging charact- eristics of 188Re labeled insulin-like growth factor 1 analogue QSSRe-IGF-1A）in tumor-bearing mice. Methods （1）To label IGF-1A with raRe directly and to determine the labeling efficiency. （2）To establish nude mice model which bearing human pancreatic carcinoma cell Patu8988. （3）To scan those nude mice at 15 min, 1 h, 4 h, 24 h, 3 d and 5 d after intratumor injection with 188Re-IGF-1A into their tumors. （4）To scan those nude mice at 15 min, 1 h, 2 h, 4 h and 24 h after intratumor injection with 188ReO4- into their tumors. To calculate the tumor to normal tissue ratio （T/NT） and the percentages of injected dose per gram tissue（%ID/g） of different organs. Results （1）The labeling efficiency of 188Re-IGF-1A was （94.07 ±0.32） %. （2）The largest uptake of tumors was （42.38±17.82） %ID/g at 4 h after injection of lSSRe-IGF-1A. Then the tumor to normal tissue ratios increased and the largest tumor to muscle ratio was 6531.79±4930.26 at 5 d after injection. （3）188ReO4- was major distributed in thyroid glands, stomachs, tumors and blood in nude mice after injection at first. Then %ID/g decreased rapidly in tumors. （4）The difference of %ID/g was significant （t=5.877, t= 13.287, P〈0.01） in tumors and kidneys between 188Re-IGF-1A group than in 188ReO4- group. The largest ratio of tumors in the two groups was 74.10 at 24 h after injection. （5）After being injected, 188Re-IGF-1A formed clear images in tumors, 5 d later, nothing but tumors can be seen. Conclusions 188Re -IGF-1A has good affinity with human pancreatic cancer, and the tumor to muscle ratios in nude mice is high. So 188Re-IGF-1A is expected to be used for targeting therapy of human pancreatic carcinoma.