Fibroblast activation protein peptide-targeted NIR-I/II fluorescence imaging for stable and functional detection of hepatocellular carcinoma
文献类型：期刊论文
| 作者 | Lin, En5,6; Song, Miaomiao2; Wang, Bo5,6; Shi, Xiaojing4,5; Zhao, Jiali6; Fu, Lidan4,5; Bai, Zirui6; Zou, Baojia6; Zeng, Guifang6; Zhuo, Wenfeng6 |
| 刊名 | EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
 |
| 出版日期 | 2025-01-21 |
| 页码 | 14 |
| 关键词 | Hepatocellular carcinoma Cancer-associated fibroblasts Fibroblast activation protein Near-infrared fluorescence Peptide-targeted fluorescence imaging |
| ISSN号 | 1619-7070 |
| DOI | 10.1007/s00259-025-07093-6 |
| 英文摘要 | PurposeCancer-associated fibroblasts (CAFs) are the primary stromal component of the tumor microenvironment in hepatocellular carcinoma (HCC), affecting tumor progression and post-resection recurrence. Fibroblast activation protein (FAP) is a key biomarker of CAFs. However, there is limited evidence on using FAP as a target in near-infrared (NIR) fluorescence imaging for HCC. Thus, this study aims to develop a novel NIR fluorescent imaging strategy targeting FAP+ CAFs in HCC. MethodsThe ICG-FAP-TATA probe was synthesized by conjugating a novel cyclization anti-FAP peptide with an indocyanine green derivative (ICG-NH2) as fluorophore, capable for NIR window I (NIR-I, 700-900 nm) and II (NIR-II, 1000-1700 nm) imaging. Its efficacy in lesion localization and other potential applications was evaluated. ResultsIn vivo imaging of subcutaneous HCC models revealed that ICG-FAP-TATA specifically targeted FAP+ CAFs in the stroma and detected differences in CAFs loading within lesions. The fluorescence intensity/tumor-to-background ratio (TBR) positively correlated with FAP expression (R2 > 0.8, p < 0.05). Ex vivo incubation of tumor tissues with ICG-FAP-TATA provided stable fluorescence imaging of tumors in subcutaneous and orthotopic HCC models, including different cell line co-culture systems (LM3-luc, MHCC97H-luc, HepG2-luc + LX2), and various liver backgrounds (healthy/fibrotic) (n = 5 per group). TBR of the tumor mice models was higher for NIR-II than NIR-I imaging (3.89 +/- 1.27 vs. 2.64 +/- 0.64, p < 0.05). Moreover, NIR-I/II imaging of fresh tissues from seven patients with HCC undergoing surgery incubated with ICG-FAP-TATA visually provided the spatial distribution heterogeneity of CAFs. The targeted fluorescence was relatively enriched more in the blood flow direction and at the tumor edge, both of which were associated with tumor metastasis (all p < 0.05). ConclusionThis study presents a rapid and effective method for detecting HCC lesions, locating FAP+ CAFs, and visualizing high-risk areas for tumor metastasis at the macroscopic level. It offers a new promising approach with translational potential for imaging HCC. |
| WOS关键词 | CANCER |
| 资助项目 | National Natural Science Foundation of China (NSFC) ; Multimodal Biomedical Imaging Experimental Platform, Institute of Automation, Chinese Academy of Sciences and Molecular Imaging Center, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences |
| WOS研究方向 | Radiology, Nuclear Medicine & Medical Imaging |
| 语种 | 英语 |
| WOS记录号 | WOS:001402149900001 |
| 出版者 | SPRINGER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315989]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Cheng, Zhen; Hu, Zhenhua; Li, Jian |
| 作者单位 | 1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China 2.Chinese Acad Sci, Mol Imaging Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Chinese Peoples Liberat Army Gen Hosp, Natl Clin Res Ctr Kidney Dis, Natl Key Lab Kidney Dis, Beijing Key Lab Kidney Dis Res,Dept Nephrol,Med C, Beijing 100853, Peoples R China 4.Univ Chinese Acad Sci, Sch Artificial Intelligence, Beijing, Peoples R China 5.Chinese Acad Sci, Inst Automat, CAS Key Lab Mol Imaging, Beijing Key Lab Mol Imaging, 95 Zhongguancun East Rd, Beijing 100190, Peoples R China 6.Sun Yat Sen Univ, Affiliated Hosp 5, Liver Transplantat Ctr, Dept Hepatobiliary Surg, 52 Mei Hua East Rd, Zhuhai 519000, Peoples R China |
| 推荐引用方式 GB/T 7714 | Lin, En,Song, Miaomiao,Wang, Bo,et al. Fibroblast activation protein peptide-targeted NIR-I/II fluorescence imaging for stable and functional detection of hepatocellular carcinoma[J]. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,2025:14. |
| APA | Lin, En.,Song, Miaomiao.,Wang, Bo.,Shi, Xiaojing.,Zhao, Jiali.,...&Li, Jian.(2025).Fibroblast activation protein peptide-targeted NIR-I/II fluorescence imaging for stable and functional detection of hepatocellular carcinoma.EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,14. |
| MLA | Lin, En,et al."Fibroblast activation protein peptide-targeted NIR-I/II fluorescence imaging for stable and functional detection of hepatocellular carcinoma".EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING (2025):14. |
入库方式： OAI收割
来源：上海药物研究所
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