Optical magnetic multimodality imaging of plectin-1-targeted imaging agent for the precise detection of orthotopic pancreatic ductal adenocarcinoma in mice
Wenjia Zhang,
Xiaolong Liang,
Liang Zhu,
Xinyu Zhang,
Zhengyu Jin,
Yang Du,
Jie Tian,
Huadan Xue
Affiliations
Wenjia Zhang
Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dong Cheng District, Beijing 100730, China; CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Hai Dian District, Beijing 100190, China
Xiaolong Liang
Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China
Liang Zhu
Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dong Cheng District, Beijing 100730, China
Xinyu Zhang
Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dong Cheng District, Beijing 100730, China
Zhengyu Jin
Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dong Cheng District, Beijing 100730, China; Corresponding author at: Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dong Cheng District, Beijing 100730, China
Yang Du
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Hai Dian District, Beijing 100190, China; The University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding author at: CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Hai Dian District, Beijing 100190, China.
Jie Tian
CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Hai Dian District, Beijing 100190, China; Beijing Advanced Innovation Centre for Big Data-Based Precision Medicine, School of Medicine, Beihang University, Beijing 100191, China; Corresponding author at: CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, the State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, No. 95 Zhongguancun East Road, Hai Dian District, Beijing 100190, China.
Huadan Xue
Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dong Cheng District, Beijing 100730, China; Corresponding author at: Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dong Cheng District, Beijing 100730, China
Summary: Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy worldwide, and the precise detection is challenging currently. Magnetic particle imaging (MPI) is suitable for imaging deep and internal PDAC tumours because of its high sensitivity and unlimited imaging depth. The purpose of this study was to utilize the MPI, in combination with fluorescence molecular imaging (FMI) and magnetic resonance imaging (MRI), to advance the in vivo precise detection of PDAC xenografts. Methods: The PDAC targeted plectin-1 peptide and IRDye800CW were conjugated to the superparamagnetic iron oxide nanoparticles (PTP-Fe3O4-IRDye800CW) for the PDAC-targeting triple-modality imaging. Subcutaneous and orthotopic PDAC mouse models were established. FMI, MPI, and MRI were performed for dynamic and quantitative observation of PDAC tumours. Histological staining analyses were used for ex vivo validation. Findings: PTP-Fe3O4-IRDye800CW nanoparticles possessed great triple-modality imaging performance and specific targeting to plectin-1 expressed on PDAC cells. For in vivo multi-modality imaging of orthotopic PDAC models, the PTP-Fe3O4-IRDye800CW nanoparticles demonstrated higher specificity, even distribution, and longer retention effects in tumours for over 7 d compared with Con-Fe3O4-IRDye800CW nanoparticles. (MPI, 2d post-injection: PTP-Fe3O4-IRDye800CW: 85.72% ± 1.53% vs. Con-Fe3O4-IRDye800CW: 74.41% ± 1.91%, **P < 0.01 (Student's t test)). Ex vivo histological and Prussian blue stainings were performed to validate the distribution of probes. Interpretation: These data demonstrate the feasibility of utilizing MPI for in vivo PDAC imaging and complement with FMI/MRI for a precise and comprehensive in vivo characterization of PDAC. This may benefit PDAC patients for precise diagnosis and guidance of therapy. Funding: This study was funded by the National Natural Science Foundation of China (Grant No. 62027901, 82071896, 81871422, 81871514, 81227901), Ministry of Science and Technology of China under Grant No. 2017YFA0205200, 2017YFA0700401, Beijing Natural Science Foundation (Grant No. 7212207), Elite Program of Dong Cheng District of Beijing (2020-dchrcpyzz-28), and Peking University Third Hospital (BYSYZD2019018, and jyzc2018-02).
