Efficacy of 177Lu-PSMA-I&T in the treatment of prostate cancer / 中华核医学与分子影像杂志

ABSTRACT

Objective:To evaluate the therapeutic effect of 177Lu-prostate specific membrane antigen (PSMA)-I&T on prostate cancer. Methods:The culture medium of 1.85, 18.50, 185.00, 555.00 and 925.00 MBq/L 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 MBq 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 MBq 177Lu-PSMA-I&T for 48 h to detect cell apoptosis. Tumor-bearing mice models were established (BALB/c-nu/nu nude mice, 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 t test and paired t test were used to analyze the data. Results:Compared with the control group ((100.00±12.35)%), the cell survival rates were significantly decreased after 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)%; F=78.91, t values 8.312-14.106, all P<0.01). Cell survival rates were significantly reduced in 185.00 MBq/L group at different time points (24, 48 and 72 h; F=78.28, t values 6.628-14.384, all P<0.01). The proportion of LNCaP cells in G2/M phase was increased from (12.36±0.28)% to (19.92±0.48)% ( t=17.180, P<0.01). The apoptosis rates of cells were significantly increased in 18.5 and 37.0 MBq groups ( F=71.86, t values -6.138, -13.050, both 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±13.8 vs 240.3±3.7; F=78.20, t values 7.549-13.345, all 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)% vs (14.89±3.80)%, (5.60±1.83)%, (3.46±0.71)%) and TUNEL-fluorescein isothiocyanate (TUNEL-FITC) staining ((0.74±0.18)% 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 ( F=103.91, t values 10.429-15.762; F=38.66, t values from -9.312 to -2.881, all P<0.01). Conclusions:177Lu-PSMA-I&T has a good therapeutic effect on prostate cancer, with no obvious therapeutic side effects. Therefore, 177Lu-PSMA-I&T is expected to be an ideal drug for treating prostate cancer.