目的:评价n 177Lu-前列腺特异膜抗原(PSMA)-I&T对前列腺癌的治疗效果。n 方法:将1.85、18.50、185.00、555.00和925.00 MBq/L n 177Lu-PSMA-I&T培养液加入LNCaP细胞(200 μl/孔，5个实验组，1个对照组，每组3个复孔)培养24 h后，检测各组细胞存活率。将3.7 MBqn 177Lu-PSMA-I&T培养液加入LNCaP细胞(1个实验组，1个对照组，每组3个复孔)培养48 h，检测细胞周期变化。将3.7、19.5和37.0 MBqn 177Lu-PSMA-I&T培养液加入LNCaP细胞(3个实验组，1个对照组，每组设3个复孔)培养48 h，检测细胞凋亡。构建荷瘤裸鼠模型(BALB/c-nu/nu裸鼠，32只)。n 177Lu-PSMA-I&T治疗后20 d内，观察荷瘤裸鼠肿瘤体积及体质量变化。治疗后第7天，对荷瘤裸鼠肿瘤组织行HE染色、细胞增殖核抗原Ki-67蛋白免疫组织荧光染色及原位末端标记(TUNEL)法检测细胞凋亡。治疗后第20天，对荷瘤裸鼠主要器官行病理分析。采用单因素方差分析、最小显著差异n t检验、配对n t检验分析数据的差异。n 结果:177Lu-PSMA-I&T干预后，185.00、555.00和925.00 MBq/L组LNCaP细胞存活率[(57.56±6.35)%、(38.65±3.39)%和(27.95±4.48)%]均较对照组[(100.00±12.35)%]降低(n F＝78.91，n t值：8.312～14.106，均n P<0.01)，185.00 MBq/L组不同时间点(24、48和72 h)的细胞存活率低于对照组(0 h)(n F＝78.28，n t值：6.628～14.384，均n P<0.01)；G2/M期的LNCaP细胞占比从(12.36±0.28)%上升至(19.92±0.48)%(n t＝17.180, n P<0.01)；18.5和37.0 MBq组细胞凋亡率明显增高(n F＝71.86，n t值：-6.138和-13.050，均n P<0.01)。3.7、14.8、29.6 MBq组与对照组(0 MBq)间荷瘤裸鼠相对肿瘤体积(RTV%)差异均有统计学意义(136.7±7.4、59.2±23.8和47.3±13.8与240.3±3.7；n F＝78.20，n t值：7.549～13.345，均n P<0.01)；但体质量均无明显变化。3.7、14.8和29.6 MBq组肿瘤组织Ki-67染色细胞阳性率[(14.89±3.80)%、(5.60±1.83)%和(3.46±0.71)%]及TUNEL-异硫氰酸荧光素(TUNEL-FITC)染色阳性率[(1.61±0.30)%、(3.19±0.44)%和(3.54±0.47)%]与对照组[(37.23±3.04)%和(0.74±0.18)%]的差异均有统计学意义(n F＝103.91, n t值：10.429～15.762; n F＝38.66，n t值：-9.312～-2.881，均n P<0.01)。n 结论:177Lu-PSMA-I&T对前列腺癌治疗效果好，无明显治疗不良反应，有望成为治疗前列腺癌的理想药物。n “,”Objective:To evaluate the therapeutic effect of n 177Lu-prostate specific membrane antigen (PSMA)-I&T on prostate cancer.n Methods:The culture medium of 1.85, 18.50, 185.00, 555.00 and 925.00 MBq/L n 177Lu-PSMA-I&T was added into LNCaP cells (200 μl/well, 5 experimental groups and 1 control group, 3 replicates in each group) for 24 h, and the cell viability in each group was detected. The culture medium of 3.7 MBqn 177Lu-PSMA-I&T was added into LNCaP cells (1 experimental group, 1 control group, 3 replicates in each group) for 48 h to detect the changes of cell cycle. LNCaP cells (3 experimental groups and 1 control group, 3 replicates in each group) were added into the culture medium of 3.7, 19.5 and 37.0 MBqn 177Lu-PSMA-I&T for 48 h to detect cell apoptosis. Tumor-bearing mice models were established (BALB/c-nu/nu nude mice,n n=32). The changes of tumor volume and body mass of tumor-bearing mice were observed within 20 d after treatment. On the 7th day after treatment, tumor tissues of tumor-bearing mice were stained with HE staining and fluorescently stained with Ki-67 protein, and apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) assay. On the 20th day after treatment, pathological analysis was performed on the main viscera of the tumor-bearing mice. One-way analysis of variance, the least significant difference n t test and paired n t test were used to analyze the data.n Results:Compared with the control group ((100.00±12.35)%), the cell survival rates were significantly decreased after n 177Lu-PSMA-I&T intervention in 185.00, 555.00, 925.00 MBq/L groups ((57.56±6.35)%, (38.65±3.39)%, (27.95±4.48)%;n F=78.91, n t values: 8.312-14.106, all n P<0.01). Cell survival rates were significantly reduced in 185.00 MBq/L group at different time points (24, 48 and 72 h;n F=78.28, n t values: 6.628-14.384, all n P<0.01). The proportion of LNCaP cells in G2/M phase was increased from (12.36±0.28)% to (19.92±0.48)% (n t=17.180, n P<0.01). The apoptosis rates of cells were significantly increased in 18.5 and 37.0 MBq groups (n F=71.86, n t values: -6.138, -13.050, both n P<0.05). The difference of relative tumor volume (RTV%) was statistically significant among 3.7, 14.8 and 29.6 MBq groups and control group (136.7±7.4, 59.2±23.8, 47.3±13.8n vs 240.3±3.7; n F=78.20, n t values: 7.549-13.345, all n P<0.01). But there was no significant difference in body mass of tumor-bearing mice among groups. Compared with the control group, the positive rates of Ki-67 staining cells ((37.23±3.04)%n vs (14.89±3.80)%, (5.60±1.83)%, (3.46±0.71)%) and TUNEL-fluorescein isothiocyanate (TUNEL-FITC) staining ((0.74±0.18)% n vs (1.61±0.30)%, (3.19±0.44)%, (3.54±0.47)%) in tumor tissues of 3.7, 14.8 and 29.6 MBq groups were statistically significant (n F=103.91, n t values: 10.429-15.762; n F=38.66, n t values: from -9.312 to -2.881, all n P<0.01).n Conclusions:177Lu-PSMA-I&T has a good therapeutic effect on prostate cancer, with no obvious therapeutic side effects. Therefore,n 177Lu-PSMA-I&T is expected to be an ideal drug for treating prostate cancer.n