The Synergy of 177Lu-FAPI-046 with Tyrosine Kinase Inhibitor in a Sarcoma Patient-Derived Xenograft Mouse Model

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

doi:10.1016/j.bj.2024.100744

The Synergy of ¹⁷⁷Lu-FAPI-046 with Tyrosine Kinase Inhibitor in a Sarcoma Patient-Derived Xenograft Mouse Model

Biomed J. 2024 May 8:100744. doi: 10.1016/j.bj.2024.100744. Online ahead of print.

Authors

Jing-Ren Tseng¹, Cheng-Lung Hsu², Hsin-Hua Hsieh³, Kung-Chu Ho⁴, Yi-Hsiu Chung⁵, Chun-Yi Wu⁶

Affiliations

¹ Department of Nuclear Medicine, New Taipei Municipal TuCheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City 236, Taiwan; School of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
² Department of Hematology-Oncology, Chang Gung Memorial Hospital, Medical College of Chang Gung University, Taoyuan, Taiwan.
³ Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei Branch, Taipei.
⁴ Department of Nuclear Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
⁵ Department of Medical Research and Development, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan. Electronic address: stella720905@gmail.com.
⁶ Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei Branch, Taipei. Electronic address: chunyiwu@nycu.edu.tw.

PMID: 38729609
DOI: 10.1016/j.bj.2024.100744

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.

Keywords: (177)Lu-FAPI-46; Sarcoma; fibroblast activation protein (FAP); patient-derived xenograft (PDX).