The synergy of 177Lu-FAPI-46 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

Biomedical Journal (Jun 2024)

The synergy of 177Lu-FAPI-46 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

Affiliations

Jing-Ren Tseng: Department of Nuclear Medicine, New Taipei Municipal TuCheng Hospital (Built and Operated by Chang Gung Medical Foundation), New Taipei City, Taiwan; School of Medicine, Chang Gung University, Taoyuan, Taiwan
Cheng-Lung Hsu: Department of Hematology-Oncology, Chang Gung Memorial Hospital, Medical College of Chang Gung University, Taoyuan, Taiwan
Hsin-Hua Hsieh: Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan
Kung-Chu Ho: Department of Nuclear Medicine, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
Yi-Hsiu Chung: Department of Medical Research and Development, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Corresponding author. Department of Medical Research and Development, Chang Gung Memorial Hospital at Linkou, No.5, Fuxing St., Guishan Dist., Taoyuan City 333, Taiwan.
Chun-Yi Wu: Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan; Corresponding author. Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, 155 Li-Nong St., Sec. 2, Beitou, Taipei, 112, Taiwan.

Journal volume & issue: Vol. 47, no. 3
p. 100744

Abstract

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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.

Published in Biomedical Journal

ISSN: 2319-4170 (Print); 2320-2890 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: https://www.sciencedirect.com/journal/biomedical-journal

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