Construction of 177Lu-labeled affibody radiopharmaceutical targeting HER2 and its evaluation in tumor xenografts
10.3760/cma.j.cn321828-20240318-00106
- VernacularTitle:靶向HER2的 177Lu标记亲和体核素药物的构建及其在荷瘤鼠中的评估
- Author:
Jiayue LIU
1
;
Xiaoyi GUO
;
Hua ZHU
;
Zhi YANG
Author Information
1. 北京大学肿瘤医院暨北京市肿瘤防治研究所核医学科、国家药监局放射性药物研究与评价重点实验室、恶性肿瘤发病机制及转化研究教育部重点实验室，北京 100142
- Keywords:
Stomach neoplasms;
Genes, erbB-2;
Isotope labeling;
Lutetium;
Trastuzumab;
Mice, Nude
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2024;44(6):324-329
- CountryChina
- Language:Chinese
-
Abstract:
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-tetraacetic 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 treatment of HER2-positive tumor. Methods:177Lu labeling was accomplished by using a hydrochloric acid-sodium acetate buffer system. The radiochemical purity and in vitro stability of the labeled products were analyzed by radio high performance liquid chromatography. Biodistribution, 177Lu-DOTA-HER2-BCH radionuclide targeting therapy, and trastuzumab therapy were performed in the HER2-positive NCI-N87 tumor-bearing mice. Repeated measures analysis of variance and Bonferroni method were utilized to analyze data. Results: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 targeted, with high tumor uptake and high retention. The tumor uptake values at 4, 24, 72 and 96 h post-injection 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 significantly 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 mm 3;F=4.02, P=0.016 (Bonferroni correction method), and then differences of tumor volume between the 2 groups increased with time. The differences of tumor volume between 177Lu-DOTA-HER2-BCH and trastuzumab treatment 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:177Lu-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.
