Magnetic-optical dual-modality imaging monitoring chemotherapy efficacy of pancreatic ductal adenocarcinoma with a low-dose fibronectin-targeting Gd-based contrast agent

doi:10.1007/s00259-024-06617-w

CORC > 自动化研究所 > 中国科学院自动化研究所 > 中国科学院分子影像重点实验室

	Magnetic-optical dual-modality imaging monitoring chemotherapy efficacy of pancreatic ductal adenocarcinoma with a low-dose fibronectin-targeting Gd-based contrast agent
	Zhang, Wenjia 1,2,3; Liang, Xiaolong 4; Zhang, Xinyu 1; Tong, Wei 3; Shi, Guangyuan 3; Guo, Haozhuo 3; Jin, Zhengyu 1; Tian, Jie 3,5; Du, Yang 3,6; Xue, Huadan 1
刊名	EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
	2024-02-19
页码	15
关键词	Molecular imaging Magnetic resonance imaging Fluorescence molecular imaging Pancreatic cancer Fibronectin
ISSN号	1619-7070
DOI	10.1007/s00259-024-06617-w
通讯作者	Jin, Zhengyu(jinzy@pumch.cn) ; Tian, Jie(jie.tian@ia.ac.cn) ; Du, Yang(yang.du@ia.ac.cn) ; Xue, Huadan(bjdanna95@163.com)
英文摘要	Purpose Pancreatic ductal adenocarcinoma (PDAC) is a lethal hypovascular tumor surrounded by dense fibrosis. Albumin-bound paclitaxel and gemcitabine (AG) chemotherapy is the mainstay of PDAC treatment through depleting peritumoral fibrosis and killing tumor cells; however, it remains challenging due to the lack of a noninvasive imaging method evaluating fibrotic changes during AG chemotherapy. In this study, we developed a dual-modality imaging platform that enables noninvasive, dynamic, and quantitative assessment of chemotherapy-induced fibrotic changes through near-infrared fluorescence molecular imaging (FMI) and magnetic resonance imaging (MRI) using an extradomain B fibronectin (EDB-FN)-targeted imaging probe (ZD2-Gd-DOTA-Cy7). Methods The ZD2-Gd-DOTA-Cy7 probe was constructed by conjugating a peptide (Cys-TVRTSAD) to Gd-DOTA and the near-infrared dye Cy7. PDAC murine xenograft models were intravenously injected with ZD2-Gd-DOTA-Cy7 at a Gd concentration of 0.05 mmol/kg or free Cy7 and Gd-DOTA as control. The normalized tumor background ratio (TBR) on FMI and the T1 reduction ratio on MRI were quantitatively analyzed. For models receiving AG chemotherapy or saline, MRI/FMI was performed before and after treatment. Histological analyses were performed for validation. Results The ZD2-Gd-DOTA-Cy7 concentration showed a linear correlation with the fluorescence intensity and T1 relaxation time in vitro. The optimal imaging time was 30 min after injection of the ZD2-Gd-DOTA-Cy7 (0.05 mmol/kg), only half of the clinic dosage of gadolinium. Additionally, ZD2-Gd-DOTA-Cy7 generated a 1.44-fold and 1.90-fold robust contrast enhancement compared with Cy7 (P < 0.05) and Gd-DOTA (P < 0.05), respectively. For AG chemotherapy monitoring, the T1 reduction ratio and normalized TBR in the fibrotic tumor areas were significantly increased by 1.99-fold (P < 0.05) and 1.78-fold (P < 0.05), respectively, in the control group compared with those in the AG group. Conclusion MRI/FMI with a low dose of ZD2-Gd-DOTA-Cy7 enables sensitive imaging of PDAC and the quantitative assessment of fibrotic changes during AG chemotherapy, which shows potential clinical applications for precise diagnosis, post-treatment monitoring, and disease management.
资助项目	National Natural Science Foundation of China[62027901] ; National Natural Science Foundation of China[82272111] ; National Natural Science Foundation of China[92159303] ; National Natural Science Foundation of China[82071896] ; National Natural Science Foundation of China[81871422] ; National Natural Science Foundation of China[81871514] ; National Natural Science Foundation of China[81227901] ; National Natural Science Foundation of China[7212207] ; National Natural Science Foundation of China[7244524] ; Beijing Natural Science Foundation[2022-PUMCH-D-001] ; National High Level Hospital Clinical Research Funding[BYSYZD2019018] ; National High Level Hospital Clinical Research Funding[jyzc2018-02] ; Peking University Third Hospital
WOS关键词	NAB-PACLITAXEL ; STELLATE CELLS ; CANCER ; PEPTIDE
WOS研究方向	Radiology, Nuclear Medicine & Medical Imaging
语种	英语
出版者	SPRINGER
WOS记录号	WOS:001164998800002
资助机构	National Natural Science Foundation of China ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; National High Level Hospital Clinical Research Funding ; Peking University Third Hospital
内容类型	期刊论文
源URL	[http://ir.ia.ac.cn/handle/173211/57798]
专题	自动化研究所_中国科学院分子影像重点实验室
通讯作者	Jin, Zhengyu; Tian, Jie; Du, Yang; Xue, Huadan
作者单位	1.Chinese Acad Med Sci & Peking Union Med Coll, Peking Union Med Coll Hosp, Dept Radiol, State Key Lab Complex Severe & Rare Dis, 1 Shuaifuyuan, Beijing 100730, Peoples R China 2.Peking Univ Peoples Hosp, Dept Radiol, Beijing 100032, Peoples R China 3.Chinese Acad Sci, State Key Lab Management & Control Complex Syst, Beijing Key Lab Mol Imaging, CAS Key Lab Mol Imaging,Inst Automat, 95 Zhongguancun East Rd, Beijing 100190, Peoples R China 4.Peking Univ Third Hosp, Dept Ultrasound, Beijing 100191, Peoples R China 5.Beihang Univ, Beijing Adv Innovat Ctr Big Data Based Precis Med, Sch Med, Beijing 100191, Peoples R China 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Wenjia,Liang, Xiaolong,Zhang, Xinyu,et al. Magnetic-optical dual-modality imaging monitoring chemotherapy efficacy of pancreatic ductal adenocarcinoma with a low-dose fibronectin-targeting Gd-based contrast agent[J]. EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,2024:15.
APA	Zhang, Wenjia.,Liang, Xiaolong.,Zhang, Xinyu.,Tong, Wei.,Shi, Guangyuan.,...&Xue, Huadan.(2024).Magnetic-optical dual-modality imaging monitoring chemotherapy efficacy of pancreatic ductal adenocarcinoma with a low-dose fibronectin-targeting Gd-based contrast agent.EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING,15.
MLA	Zhang, Wenjia,et al."Magnetic-optical dual-modality imaging monitoring chemotherapy efficacy of pancreatic ductal adenocarcinoma with a low-dose fibronectin-targeting Gd-based contrast agent".EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING (2024):15.