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.
Department of Ultrasound, Peking University Third Hospital, Beijing 100191, China.
EBioMedicine. 2022 Jun;80:104040. doi: 10.1016/j.ebiom.2022.104040. Epub 2022 May 4.
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.
The PDAC targeted plectin-1 peptide and IRDye800CW were conjugated to the superparamagnetic iron oxide nanoparticles (PTP-FeO-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.
PTP-FeO-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-FeO-IRDye800CW nanoparticles demonstrated higher specificity, even distribution, and longer retention effects in tumours for over 7 d compared with Con-FeO-IRDye800CW nanoparticles. (MPI, 2d post-injection: PTP-FeO-IRDye800CW: 85.72% ± 1.53% vs. Con-FeO-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.
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.
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).
胰腺导管腺癌（PDAC）是一种全球范围内致命的恶性肿瘤，目前其精确检测具有挑战性。磁共振粒子成像（MPI）由于其高灵敏度和无限的成像深度，非常适合对深部和内部 PDAC 肿瘤进行成像。本研究旨在利用 MPI 结合荧光分子成像（FMI）和磁共振成像（MRI），提高 PDAC 异种移植的体内精确检测。
PDAC 靶向 plectin-1 肽和 IRDye800CW 与超顺磁性氧化铁纳米颗粒（PTP-FeO-IRDye800CW）偶联，用于 PDAC 靶向三模态成像。建立了皮下和原位 PDAC 小鼠模型。进行 FMI、MPI 和 MRI 以动态和定量观察 PDAC 肿瘤。进行组织学染色分析以进行离体验证。
PTP-FeO-IRDye800CW 纳米颗粒具有出色的三模态成像性能和对 PDAC 细胞上表达的 plectin-1 的特异性靶向。对于原位 PDAC 模型的体内多模态成像，与 Con-FeO-IRDye800CW 纳米颗粒相比，PTP-FeO-IRDye800CW 纳米颗粒在肿瘤中的特异性更高，分布更均匀，保留效果更长，超过 7d。（MPI，注射后 2d：PTP-FeO-IRDye800CW：85.72%±1.53%vs.Con-FeO-IRDye800CW：74.41%±1.91%，**P<0.01（Student's t 检验））。进行离体组织学和普鲁士蓝染色以验证探针的分布。
这些数据表明，MPI 可用于体内 PDAC 成像，并与 FMI/MRI 结合，对 PDAC 进行精确和全面的体内特征描述。这可能有利于 PDAC 患者的精确诊断和治疗指导。
本研究由中国国家自然科学基金（Grant No. 62027901、82071896、81871422、81871514、81227901）、中国科学技术部（Grant No. 2017YFA0205200、2017YFA0700401）、北京市自然科学基金（Grant No. 7212207）、北京市东城区精英人才项目（2020-dchrcpyzz-28）和北京大学第三医院（BYSYZD2019018 和 jyzc2018-02）资助。
