^68Ga—DOTA—cRGD的制备及对荷肺腺癌裸鼠的显像研究

Preparation of ^68Ga-DOTA-cRGD and its utility for lung adenocarcinoma bearing nude mice imaging

目的制备^68Ga—DOTA-环RGD（cRGD），评价其在正常小鼠体内的生物分布．并进行荷肺腺癌裸鼠的靶向显像。方法以HEPES为缓冲体系（pH值5．0），水浴合成。Ga—DOTA—cRGD。采用HPLC法测定其标记率及放化纯，观察其在正常小鼠体内的生物分布。建立荷A549肺腺癌裸鼠模型，并行^68Ga-DOTA-cRGD microPET显像，勾画ROI，计算T／NT比值。用免疫组织化学及流式细胞术检测αvβ3表达水平。结果^68Ga—DOTA—cRGD的标记率为（97.8±0．1）％，标记后2h其放化纯仍高达95％。正常小鼠体内生物分布结果显示，该标记化合物血液清除迅速。5和120min血液放射性摄取值分别为（1．65±0．85）％ID／g和（0．06±0．02）％ID／g，主要经肾脏排泄，肝、胃和肠道摄取较少。荷肺腺癌裸鼠microPET显像可见肿瘤部位有放射性浓聚影，注射^68Ga—DOTA—cRGD后60min的T／NT比值最高达5．93±0．43。免疫组织化学及流式细胞分析结果均提示，肺腺癌瘤组织中有αvβ3表达。结论^68Ga-DOTA-cRGD的标记率和放化纯高，体外稳定性好，生物分布特性良好，对αvβ3阳性肺腺癌具有较好的靶向诊断性。

Objective To synthesize ^68Ga-DOTA-cyclic RDG （cRGD） , to evaluate its biodistribution in nomal mice, and to perform ^68Ga-DOTA-cRGD microPET imaging on nude mice bearing lung adenocarcinoma （LA） xenografts. Methods 6s Ga-DOTA-cRGD was synthesized in HEPES buffer system （pH 5.0）. The radiolabeled yield and radioehemistry purity were measured with HPLC. The biodistribution in the normal mice was investigated. ^68Ga-DOTA-cRGD was injected into nude mice bearing A549 LA via tail vein. Dynamic and static images were acquired using microPET. ROI was drawn to calculate the T/NT ratio. The expression of αvβ3 in LA xenografts was observed by immunohistochemistry and flow cytometry. Results The radiolabeling yield was （97.8±0.1）% and the radiochemical purity was 95% after 2 h. The biodistribution in normal mice showed rapid clearance from blood, the blood uptakes of 6SGa-DOTA-cRGD were （ 1.65±0. 85） %ID/g and （0.06±0.02） %ID/g at 5 and 120 rain postinjection. ^68Ga-DOTA-cRGD was excreted mainly via kidney, and little radioactivity were accumulated in the liver and gastrointestinal tract. Marked uptake of ^68Ga-DOTA-cRGD was found in tumor tissue of the nude mice bearing LA with maximum T/NT ratio of 5.93±0.43 at 60 min postinjection. The expression of αvβ3 was observed on LA xenograft tissues. Conclusions ^68Ga-DOTA-cRGD can be easily prepared with high radiolabeling yield and radiochemieal purity. The good stability and biodistribution characteristics make it useful for the diagnosis of human lung cancer with over expressed αvβ3 receptor.