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

IF 5.3 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics Pub Date : 2024-11-13 DOI:10.1016/j.ijpharm.2024.124946

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

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引用次数: 0

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.

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89Zr/177Lu标记的阿妥昔单抗用于胰腺导管腺癌治疗的临床前评估。

胰腺导管腺癌（PDAC）仍然是一项重大的临床挑战，迫切需要有效的干预策略。近年来，放射性药物的应用已成为准确诊断和治疗恶性肿瘤的一种有前途的方法。由于间皮素（MSLN）在胰腺癌细胞中的高表达，它已成为放射免疫疗法（RIT）的一个有吸引力的靶点。在这项研究中，我们报告了通过将阿马妥昔单抗与锆-89（89Zr）共轭而开发出的新型放射示踪剂，以促进对 MSLN 表达的无创检测。免疫正电子发射断层扫描（immunoPET）成像显示，89Zr-DFO-阿马妥昔单抗在PANC-1-MSLN肿瘤中有特异性蓄积。随后，将镥-177（177Lu）标记的阿马妥昔单抗用于MSLN靶向放射免疫疗法（RIT），结果显著抑制了PANC-1-MSLN异种移植的生长。此外，体内研究表明，177Lu-DOTA-阿马妥昔单抗的副作用有限。89Zr/177Lu标记的阿马妥昔单抗的开发可为制定针对MSLN过表达肿瘤（包括PDAC）的精准诊断和治疗策略提供新的见解。

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来源期刊

International Journal of Pharmaceutics 医学-药学

CiteScore

10.70

自引率

8.60%

发文量

951

审稿时长

72 days

期刊介绍： The International Journal of Pharmaceutics is the third most cited journal in the "Pharmacy & Pharmacology" category out of 366 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.