Development and preclinical evaluation of a gallium-68 labeled novel diagnostic tracer for visualizing ALK expression in tumor

IF 4.3 3区医学 Q1 PHARMACOLOGY & PHARMACY

European Journal of Pharmaceutical Sciences Pub Date : 2025-03-30 DOI:10.1016/j.ejps.2025.107087

Zhen-Peng Yu , Ke-Xin Sun , Dan Zhang , Zhi-Qiang Yu , Deng-Yun Chen , Hong Zhu , Hongwei Si , Peng-Fei Dai

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引用次数: 0

Abstract

Anaplastic lymphoma kinase (ALK) is prominently expressed in numerous malignant tumors, which lead to aberrant tumor proliferation, invasion and metastasis. Ceritinib (LDK378), as second-generation targeted drugs, has been used to treat advanced ALK-positive non-small cell lung cancer (NSCLC). Herein, we sought to develop a novel ALK-positron emission tomography/magnetic resonance (PET/MR) tracer ⁶⁸Ga-DOTA-CTB (⁶⁸Ga labeled ceritinib) based on ceritinib scaffold to monitor the ALK expression levels during targeted therapy with ceritinib. The ⁶⁸Ga-DOTA-CTB radiotracer, obtained via a simple labeling procedure, exhibits favorable radiochemical purity, stability, and pharmacokinetic properties. Subsequently, cellular uptake experiments have demonstrated that ⁶⁸Ga-DOTA-CTB could be accumulated in H2228 cells. Imaging and biodistribution experiments have revealed significant uptake of the radiotracer in the tumors of the experimental group, while tumors in the blocking group, which were saturated with an excess of precursor, exhibited a markedly reduced level of radioactivity. These empirical findings suggest that ⁶⁸Ga-DOTA-CTB holds substantial potential as a novel PET/MR imaging tracer for ALK-positive tumors.

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镓-68标记的新型肿瘤ALK表达诊断示踪剂的研制和临床前评价

间变性淋巴瘤激酶（ALK）在多种恶性肿瘤中显著表达，导致肿瘤异常增殖、侵袭和转移。Ceritinib （LDK378）作为第二代靶向药物，已被用于治疗晚期alk阳性非小细胞肺癌（NSCLC）。在此，我们试图开发一种基于ceritinib支架的新型ALK正电子发射断层扫描/磁共振（PET/MR）示踪剂68Ga- dota - ctb (68Ga标记的ceritinib)，以监测ceritinib靶向治疗期间ALK的表达水平。通过简单的标记程序获得的68Ga-DOTA-CTB放射性示踪剂具有良好的放射化学纯度、稳定性和药代动力学特性。随后，细胞摄取实验证明68Ga-DOTA-CTB可以在H2228细胞中积累。成像和生物分布实验显示，实验组的肿瘤明显吸收了放射性示踪剂，而阻断组的肿瘤则被过量的前体饱和，显示出明显降低的放射性水平。这些实证研究结果表明，68Ga-DOTA-CTB具有作为alk阳性肿瘤的新型PET/MR成像示踪剂的巨大潜力。

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来源期刊

European Journal of Pharmaceutical Sciences 医学-药学

CiteScore

9.60

自引率

2.20%

发文量

248

审稿时长

50 days

期刊介绍： The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.