177Lu-PSMA-I&T的自动化合成及靶向前列腺癌的实验研究

177Lu-PSMA-I&T automated radiolabeling and preclinical prostate cancer targeting research

目的自动化标记177Lu-前列腺特异膜抗原(PSMA)-I&T,评价其生物分布、药代动力学特征及对人前列腺癌LNCaP Clone FGC细胞的亲和性及靶向性。方法采用iQS-TS全自动模块标记177Lu-PSMA-I&T,测定其标记产率、放化纯及稳定性;评价其对LNCaP Clone FGC细胞的亲和性和靶向特异性;观察177Lu-PSMA-I&T在正常ICR小鼠体内的生物分布;建立人前列腺癌LNCaP Clone FGC荷瘤裸鼠模型,并于不同时间点行U-SPECT/CT显像。采用两独立样本t检验分析数据。结果177Lu-PSMA-I&T标记产率为(91.5±4.9)%,放化纯>99%,体内外稳定性好。177Lu-PSMA-I&T与LNCaP Clone FGC细胞结合的半抑制浓度为(26.74±3.53)nmol/L;LNCaP Clone FGC细胞对177Lu-PSMA-I&T的特异性摄取随时间延长不断增加,加入阻断剂后不同时间点的摄取值均降低(t值:4.301~27.483,均P<0.05)。正常ICR小鼠体内生物分布表明,177Lu-PSMA-I&T在血液清除迅速,主要经肾脏排泄。荷瘤裸鼠U-SPECT/CT显像示177Lu-PSMA-I&T在肿瘤放射性浓聚高,滞留时间长。结论iQS-TS自动化模块制备177Lu-PSMA-I&T高效简便;产物具有良好的生物学性能,对前列腺癌细胞亲和性高,是理想的靶向PSMA的前列腺癌治疗药物。

Objective To synthesis 177Lu-prostate specific membrane antigen(PSMA)-I&T with automated module,evaluate the biodistribution and pharmacokinetics in mice and study the targeting property in human prostate cancer cell line LNCaP Clone FGC.Methods The iQS-TS automated module was applied in labeling 177Lu-PSMA-I&T.Radiochemical purity and stability were determined with high performance liquid chromatography(HPLC).The biodistribution was observed in normal ICR mice and U-SPECT/CT imaging was performed in LNCaP Clone FGC tumor-bearing mice.Independent-sample t test was used to analyze the data.Results 177Lu-PSMA-I&T was stable in vitro and in vivo,with the radiolabeled yield of(91.5±4.9)%and radiochemical purity>99%.The half maximal inhibitory concentration(IC50)of 177Lu-PSMA-I&T binding to LNCaP Clone FGC cells was(26.74±3.53)nmol/L.The uptake of 177Lu-PSMA-I&T by LNCaP Clone FGC cells increased with time and significantly decreased after the inhibitor addition(t values:4.301-27.483,all P<0.05).177Lu-PSMA-I&T was cleared from blood rapidly and predominantly excreted by kidneys.Significant radioactive uptake was observed in tumors with a long retention time.Conclusion 177Lu-PSMA-I&T can be produced in a convenient and efficient procedure using iQS-TS automated module,with good biological properties and excellent affinity and targeting property towards prostate cancer cells,which making it a potential radiopharmaceutical for prostate cancer therapy.