Objective To prepare an affinity-based radionuclide therapeutic drug targeting human epidermal growth factor receptor 2(HER2),named 177Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tet-raacetic acid(DOTA)-HER2-BCH,and preliminarily evaluate its biodistribution,therapeutic efficacy,and safety in HER2-positive tumor models,in order to explore its feasibility as a radiopharmaceutical for treat-ment of HER2-positive tumor.Methods 177 Lu labeling was accomplished by using a hydrochloric acid-so-dium acetate buffer system.The radiochemical purity and in vitro stability of the labeled products were ana-lyzed by radio high performance liquid chromatography.Biodistribution,177Lu-DOTA-HER2-BCH radionu-clide targeting therapy,and trastuzumab therapy were performed in the HER2-positive NCI-N87 tumor-bear-ing mice.Repeated measures analysis of variance and Bonferroni method were utilized to analyze data.Re-sults 177Lu-DOTA-HER2-BCH was obtained,with the radiolabeling yield＞80％,radiochemical purity＞98％,and good in vitro stability.Biodistribution data showed that 177Lu-DOTA-HER2-BCH was well targe-ted,with high tumor uptake and high retention.The tumor uptake values at 4,24,72 and 96 h post-injec-tion were(11.93±0.46),(8.65±0.40),(5.89±0.69)and(3.26±0.36)percentage activity of injection dose per gram of tissue(％ID/g),respectively.In the treatment experiment,177Lu-DOTA-HER2-BCH sig-nificantly inhibited tumor growth.On the 3rd day,the tumor volume of mice treated with 177Lu-DOTA-HER2-BCH was significantly smaller than that of the control group(mean difference 146.97 mm3;F=4.02,P=0.016(Bonferroni correction method),and then differences of tumor volume between the 2 groups in-creased with time.The differences of tumor volume between 177Lu-DOTA-HER2-BCH and trastuzumab treat-ment groups were not statistically significant throughout the treatment process(F values:0.05-61.21,all P＞0.017(Bonferroni correction method)).At the end of treatment,no histological abnormality was seen in all organs of the mice.Conclusion 177 Lu-DOTA-HER2-BCH radionuclide therapy demonstrates good tumor growth inhibition in HER2-positive tumor-bearing mice,which is expected to be an alternative treatment for HER2-positive tumors.
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