The synergy of 177Lu-FAPI-46 with tyrosine kinase inhibitor in a sarcoma patient-derived xenograft mouse model

IF 4.1 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomedical Journal Pub Date : 2024-06-01 DOI:10.1016/j.bj.2024.100744

Jing-Ren Tseng , Cheng-Lung Hsu , Hsin-Hua Hsieh , Kung-Chu Ho , Yi-Hsiu Chung , Chun-Yi Wu

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Abstract

Background

Given the heterogeneity and high mortality associated with metastatic soft tissue sarcoma, this study aims to evaluate the therapeutic efficacy of combining ¹⁷⁷Lu-FAPI-46 with Pazopanib against this malignancy.

Methods

Patient-derived xenograft (PDX)-bearing mice were randomly divided into three groups: the control group, the ¹⁷⁷Lu-FAPI-46 monotherapy group, and the ¹⁷⁷Lu-FAPI-46 combined with Pazopanib therapy group. Therapeutic efficacy was regularly monitored.

Results

The microPET imaging showed a 0.84-fold decrease in the T/M ratio of 68Ga-FAPI-46 on day 7/8 post combination therapy, while the control group exhibited a 1.23-fold increase. Combination therapy significantly inhibited tumor proliferation, as evidenced by reduced Ki-67 and increased caspase 3 expressions. Notably, there was no significant body weight loss observed in any group.

Conclusion

This study successfully demonstrated the reduction in FAP expression and suppression of tumor volume in sarcoma PDX following the combination therapy of ¹⁷⁷Lu-FAPI-46 with Pazopanib.

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肉瘤患者异种移植小鼠模型中 177Lu-FAPI-046 与酪氨酸激酶抑制剂的协同作用

研究背景鉴于转移性软组织肉瘤的异质性和高死亡率，本研究旨在评估177Lu-FAPI-46与帕唑帕尼联合治疗该恶性肿瘤的疗效：患者异种移植（PDX）小鼠随机分为三组：对照组、177Lu-FAPI-46 单药治疗组和 177Lu-FAPI-46 联合帕唑帕尼治疗组。定期监测疗效：结果：microPET成像显示，联合治疗后第7/8天，68Ga-FAPI-46的T/M比值下降了0.84倍，而对照组则上升了1.23倍。联合疗法明显抑制了肿瘤的增殖，Ki-67的减少和caspase 3的增加都证明了这一点。值得注意的是，各组均未观察到明显的体重下降：本研究成功证明了 177Lu-FAPI-46 与帕唑帕尼联合治疗后，肉瘤 PDX 中 FAP 表达的减少和肿瘤体积的抑制。

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来源期刊

Biomedical Journal Medicine-General Medicine

CiteScore

11.60

自引率

1.80%

发文量

128

审稿时长

42 days

期刊介绍： Biomedical Journal publishes 6 peer-reviewed issues per year in all fields of clinical and biomedical sciences for an internationally diverse authorship. Unlike most open access journals, which are free to readers but not authors, Biomedical Journal does not charge for subscription, submission, processing or publication of manuscripts, nor for color reproduction of photographs. Clinical studies, accounts of clinical trials, biomarker studies, and characterization of human pathogens are within the scope of the journal, as well as basic studies in model species such as Escherichia coli, Caenorhabditis elegans, Drosophila melanogaster, and Mus musculus revealing the function of molecules, cells, and tissues relevant for human health. However, articles on other species can be published if they contribute to our understanding of basic mechanisms of biology. A highly-cited international editorial board assures timely publication of manuscripts. Reviews on recent progress in biomedical sciences are commissioned by the editors.