单位：[1]Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430074, China.核医学科华中科技大学同济医学院附属同济医院[2]Department of Chemistry, Johannes Gutenberg University, 55131 Mainz, Germany.[3]Department of Anatomy, School of Basic Medicine, Huazhong University of Science and Technology, Hubei Province, Wuhan 430030, China.[4]Cell Architecture Research Center, Huazhong University of Science and Technology, Hubei Province, Wuhan 430030, China.
Fibroblast activation protein (FAP) is highly expressed in many tumor types and constitutes a promising target for tumor-specific delivery of therapeutic radionuclides. [177Lu]Lu-DOTAGA.(SA.FAPi)2 is a novel radiopharmaceutical based on a novel bidentate inhibitor of FAP that is excreted more slowly than its monomeric counterparts. Still, the efficacy of radiotherapy is mitigated by cascades of DNA damage repair signaling in tumor cells including those via Poly(ADP-ribose) polymerase (PARP). We hereby aimed to evaluate the efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2 in combination with a PARP inhibitor, Olaparib, in the 4T1 murine triple negative breast cancer (TNBC) model. The therapeutic efficacy was visualized using 18F-FDG and [68Ga]Ga-FAPI-04 positron emission imaging/computer tomography (PET/CT). Our results demonstrated that Olaparib suppressed BALB/3T3 fibroblasts in vitro and sensitized the efficacy of [177Lu]Lu-DOTAGA.(SA.FAPi)2 in mice bearing 4T1 tumors via enhancement of DNA damage. Treatment-associated toxicity was tolerable with only mild leukopenia. Therefore, the combination of [177Lu]Lu-DOTAGA.(SA.FAPi)2 and Olaparib is a feasible treatment against TNBC.
基金：
This work was supported by the National Natural Science
Foundation of China (No. 82272041, 81873903, and
91959119).
语种：
外文
被引次数：
WOS：
PubmedID：
中科院(CAS)分区：
出版当年[2022]版：
大类|2 区医学
小类|2 区药学2 区医学：研究与实验
最新[2025]版：
大类|2 区医学
小类|2 区药学3 区医学：研究与实验
JCR分区：
出版当年[2021]版：
Q1PHARMACOLOGY & PHARMACYQ2MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1PHARMACOLOGY & PHARMACYQ2MEDICINE, RESEARCH & EXPERIMENTAL
第一作者单位：[1]Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430074, China.
通讯作者：
通讯机构：[1]Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430074, China.[*1]Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China
推荐引用方式(GB/T 7714)：
Bao Guangfa,Zhou Huimin,Zou Sijuan,et al.Inhibition of Poly(ADP-ribose) Polymerase Sensitizes [177Lu]Lu-DOTAGA.(SA.FAPi)2-Mediated Radiotherapy in Triple-Negative Breast Cancer[J].MOLECULAR PHARMACEUTICS.2023,20(5):2443-2451.doi:10.1021/acs.molpharmaceut.2c01051.
APA：
Bao Guangfa,Zhou Huimin,Zou Sijuan,Chen Lixing,Zhang Buchuan...&Zhu Xiaohua.(2023).Inhibition of Poly(ADP-ribose) Polymerase Sensitizes [177Lu]Lu-DOTAGA.(SA.FAPi)2-Mediated Radiotherapy in Triple-Negative Breast Cancer.MOLECULAR PHARMACEUTICS,20,(5)
MLA：
Bao Guangfa,et al."Inhibition of Poly(ADP-ribose) Polymerase Sensitizes [177Lu]Lu-DOTAGA.(SA.FAPi)2-Mediated Radiotherapy in Triple-Negative Breast Cancer".MOLECULAR PHARMACEUTICS 20..5(2023):2443-2451
