Objective To prepare a 177Lu labeled human epidermal growth factor receptor 2(HER2)affibody 177Lu-1,4,7-triazacyclononane-1,4,7-triacetic acid(NOTA)-maleimide(Mal)-cysteine(Cys)-ZHER2:342(1n Lu-NOTA-MZHER2 for short),and investigate its labeling process and anti-tumor properties.Methods Two kinds of buffer systems(sodium acetate buffer system and sodium ascorbate buffer system)were investigated.The effects of pH value,precursor mass and reaction temperature on 177Lu labe-ling NOTA-MZHER2 were compared to obtain optimal labeling conditions.The radiochemical purity of la-beled product was determined by instant thin-layer chromatography(ITLC),and its stabilities in PBS and plasma were observed.Human ovarian cancer cell line SKOV-3 was selected for cell internalization and cyto-toxicity test to evaluate cell uptake and killing effect of 177Lu-NOTA-MZHER2.SKOV-3 tumor-bearing mice(n=3)were injected with 177Lu-NOTA-MZHER2,and microSPECT/CT imaging was performed.Another 40 tumor-bearing mice were divided into 22.2 MBq group(tail vein injection with probe of 22.2 MBq),control group(tail vein injection with PBS),low-dose group(tumor injection with probe of 3.7 MBq)and high-dose group(tumor injection with probe of 7.4 MBq).Tumor volume and mass of tumor-bearing mice were monitored after injection,and the anti-tumor effect and toxicity of probe were evaluated.Repeated measure-ment analysis of variance(Bonferroni method)was used to analyze the data.Results The optimal labeling condition was 70-80 ℃ for 30 min in the system of sodium acetate buffer solution with pH=4 and precursor mass of 50 μg.Under these conditions,the labeling rate of 177Lu-NOTA-MZHER2 was(99.3±0.4)％and radiochemical purity was＞99％.After 12 d in PBS and plasma,the radiochemical purities were(95.0±1.5)％and(95.0±2.1)％.Results of cell experiment showed that the internalization of 177Lu-NOTA-MZHER2 accounted for(29.02±3.50)％of the total uptake,and the survival rate of SKOV-3 cells was(48±6)％with the probe concerntration of 6×10-3 Bq/L.SPECT imaging showed that 177Lu-NOTA-MZHER2 was still concentrated at the tumor site 96 h after injection with a dose of 18.5 MBq.Relative tumor volume(RTV)of tumor-bearing mice in 22.2 MBq group,high-dose group and low-dose group was significantly dif-ferent from that in control group(F=21.75,P＜0.001).Twenty days after injection,RTV and relative body mass of the tumor-bearing mice in high-dose group were(140±7)％and(80±9)％,respectively.Compared with control group,high-dose group had obvious anti-tumor effect(both P＜0.001).Conclusion 177Lu-NOTA-MZHER2 is successfully prepared,which is simple and efficient,and the probe has good anti-tumor effect.
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