Preclinical evaluation of 89Zr/177Lu-labeled amatuximab for theranostic application in pancreatic ductal adenocarcinoma

Zhou Lu; Mingsong Shi; Xueting Zheng; Yuanyuan Liang; Jiali Wang; Zhiyan Zou; Rui Luo; Maosen Feng; Xia Yang; Yan Zhou; Xiaoan Li

doi:10.1016/j.ijpharm.2024.124946

Preclinical evaluation of ⁸⁹Zr/¹⁷⁷Lu-labeled amatuximab for theranostic application in pancreatic ductal adenocarcinoma

Int J Pharm. 2024 Nov 12:124946. doi: 10.1016/j.ijpharm.2024.124946. Online ahead of print.

Authors

Zhou Lu¹, Mingsong Shi¹, Xueting Zheng¹, Yuanyuan Liang¹, Jiali Wang¹, Zhiyan Zou¹, Rui Luo², Maosen Feng³, Xia Yang⁴, Yan Zhou⁵, Xiaoan Li⁶

Affiliations

¹ NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China.
² Department of Nuclear Medicine, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China.
³ Department of Gastroenterology, National Clinical Key Specialty, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China.
⁴ Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang 621900, China.
⁵ NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China. Electronic address: [email protected].
⁶ NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China; Department of Gastroenterology, National Clinical Key Specialty, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang 621000, China. Electronic address: [email protected].

PMID: 39542119
DOI: 10.1016/j.ijpharm.2024.124946

Abstract

Pancreatic ductal adenocarcinoma (PDAC) remains a significant clinical challenge, urgently requiring effective intervention strategies. In recent years, the application of radiopharmaceuticals has emerged as a promising modality for the accurate diagnosis and treatment of malignancies. Due to its high expression on pancreatic cancer cells, mesothelin (MSLN) has become an appealing target for radioimmunotherapy (RIT). In this study, we report the development of a novel radiotracer by conjugating amatuximab with zirconium-89 (⁸⁹Zr) to facilitate the non-invasive detection of MSLN expression. Immuno-positron emission tomography (immunoPET) imaging demonstrated a specific accumulation of ⁸⁹Zr-DFO- amatuximab in PANC-1-MSLN tumors. Subsequently, Lutetium-177 (¹⁷⁷Lu)-labeled amatuximab was utilized for MSLN- targeted radioimmunotherapy (RIT), resulting in a significant suppression of PANC-1-MSLN xenograft growth. Furthermore, in vivo studies indicated that ¹⁷⁷Lu-DOTA-amatuximab exhibited limited side effects. The development of ⁸⁹Zr/¹⁷⁷Lu-labeled amatuximab may provide novel insights into the formulation of precision diagnostic and therapeutic strategies for MSLN- overexpressing tumors, including PDAC.

Keywords: Lutetium-177; Mesothelin; Pancreatic ductal adenocarcinoma; Theranostics; Zirconium-89.