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[68Ga]Ga-labeled FAPI Conjugated with Gly-Pro Sequence for PET Imaging of Malignant Tumors

文献类型：期刊论文

作者Shang, Yuxiang7,8; Zhang, Guojin7; Yao, Xinchao7; Lai, Chaoquan6; Wang, Fanghu7; Zeng, Baozhen5; Liu, Entao7; Yuan, Hui7; Cheng, Zhen2,3,4; Jiang, Lei1,7,8
刊名MOLECULAR IMAGING AND BIOLOGY
出版日期2024-08-01
卷号26期号:4页码:729-737
关键词Fibroblast activation protein (FAP) fibroblast activation protein inhibitor (FAPI) Gly-pro PET
ISSN号1536-1632
DOI10.1007/s11307-024-01935-9
通讯作者Cheng, Zhen(zcheng@simm.ac.cn) ; Jiang, Lei(leijiang1031@163.com)
英文摘要Purpose To improve tumor uptake and prolong tumor retention, a novel fibroblast activation protein (FAP) ligand based on a quinoline-based FAP inhibitor (FAPI) conjugated with the Gly-Pro sequence and 1,4,7,10-tetraazacyclododecane-N,N ',N '',N & tprime;-tetraacetic acid (DOTA) was radiolabeled with [Ga-68]GaCl3 ([Ga-68]Ga-DOTA-GPFAPI-04). Due to the tumor heterogeneity, this study aimed to further validate the preclinical value of [Ga-68]Ga-DOTA-GPFAPI-04 PET imaging in tumor mice models with different FAP expression levels. Methods [Ga-68]Ga-DOTA-GPFAPI-04 was synthesized and its partition coefficient was measured. The stability of [Ga-68]Ga-DOTA-GPFAPI-04 was tested in phosphate-buffered saline (PBS, pH 7.4) and fetal bovine serum (FBS). Small animal PET and semi-quantitative studies were conducted in Panc-1 and A549 xenograft tumor mice models compared with [Ga-68]Ga-DOTA-FAPI-04. Immunofluorescent and immunohistochemical staining and western blot assay were performed to confirm FAP expression in xenograft tumors. Results [Ga-68]Ga-DOTA-GPFAPI-04 exhibited a radiochemical purity of > 99% and high stability in PBS and FBS. [Ga-68]Ga-DOTA-GPFAPI-04 had higher hydrophilic property than [Ga-68]Ga-DOTA-FAPI-04 (-4.09 +/- 0.05 vs -3.45 +/- 0.05). Small animal PET and semi-quantitative analysis revealed Panc-1 xenograft tumor displayed higher tumor uptake of [Ga-68]Ga-DOTA-GPFAPI-04 and tumor-to-background ratios compared to A549 xenograft tumor, consistent with the results of immunofluorescence, immunohistochemistry, and western blot. Moreover, [Ga-68]Ga-DOTA-GPFAPI-04 demonstrated higher tumor accumulation and longer tumor retention than [Ga-68]Ga-DOTA-FAPI-04 in both Panc-1 and A549 xenograft tumors. Furthermore, the FAP-binding specificity of [Ga-68]Ga-DOTA-GPFAPI-04 was confirmed in vivo by co-injection of unlabeled GPFAPI-04. Conclusion [Ga-68]Ga-DOTA-GPFAPI-04 showed more favorable in vivo tumor imaging and longer tumor retention compared to [Ga-68]Ga-DOTA-FAPI-04, which has high potential to be a promising PET probe for detecting FAP-positive tumors.
WOS关键词FIBROBLAST ACTIVATION PROTEIN ; EXPRESSION
资助项目National Natural Science Foundation of China[81971645] ; Guangdong Provincial People's Hospital[KY0120211130] ; Gansu Science and Technology Major Project[23ZDFA014] ; Shanghai Municipal Science and Technology Major Project[TM202301H003] ; Shandong Laboratory Program[SYS202205] ; Guangdong Provincial Key Laboratory of Artificial Intelligence in Medical Image Analysis and Application[2022B1212010011]
WOS研究方向Radiology, Nuclear Medicine & Medical Imaging
语种英语
WOS记录号WOS:001269987500001
出版者SPRINGER
源URL[http://119.78.100.183/handle/2S10ELR8/312398]  
专题新药研究国家重点实验室
通讯作者Cheng, Zhen; Jiang, Lei
作者单位1.Guangdong Prov Key Lab Artificial Intelligence Med, Guangzhou, Peoples R China
2.Univ Chinese Acad Sci, Beijing, Peoples R China
3.Bohai Rim Adv Res Inst Drug Discovery, Drug Discovery Shandong Lab, Yantai, Shandong, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Mol Imaging Ctr, State Key Lab Drug Res, Shanghai, Peoples R China
5.Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, Dept Pathol, Guangzhou, Peoples R China
6.Northeastern Univ, Inst Mol Med, Coll Life & Hlth Sci, Shenyang, Peoples R China
7.Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Acad Med Sci, PET Ctr,Dept Nucl Med, Guangzhou, Peoples R China
8.Guangdong Acad Med Sci, Guangdong Prov Peoples Hosp, Guangdong Cardiovasc Inst, Guangzhou, Peoples R China
推荐引用方式
GB/T 7714		 Shang, Yuxiang,Zhang, Guojin,Yao, Xinchao,et al. [68Ga]Ga-labeled FAPI Conjugated with Gly-Pro Sequence for PET Imaging of Malignant Tumors[J]. MOLECULAR IMAGING AND BIOLOGY,2024,26(4):729-737.
APA Shang, Yuxiang.,Zhang, Guojin.,Yao, Xinchao.,Lai, Chaoquan.,Wang, Fanghu.,...&Jiang, Lei.(2024).[68Ga]Ga-labeled FAPI Conjugated with Gly-Pro Sequence for PET Imaging of Malignant Tumors.MOLECULAR IMAGING AND BIOLOGY,26(4),729-737.
MLA Shang, Yuxiang,et al."[68Ga]Ga-labeled FAPI Conjugated with Gly-Pro Sequence for PET Imaging of Malignant Tumors".MOLECULAR IMAGING AND BIOLOGY 26.4(2024):729-737.

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来源：上海药物研究所

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