Zhen-Peng Yu , Ke-Xin Sun , Dan Zhang , Zhi-Qiang Yu , Deng-Yun Chen , Hong Zhu , Hongwei Si , Peng-Fei Dai
{"title":"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","authors":"Zhen-Peng Yu , Ke-Xin Sun , Dan Zhang , Zhi-Qiang Yu , Deng-Yun Chen , Hong Zhu , Hongwei Si , Peng-Fei Dai","doi":"10.1016/j.ejps.2025.107087","DOIUrl":null,"url":null,"abstract":"<div><div>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 <sup>68</sup>Ga-DOTA-CTB (<sup>68</sup>Ga labeled ceritinib) based on ceritinib scaffold to monitor the ALK expression levels during targeted therapy with ceritinib. The <sup>68</sup>Ga-DOTA-CTB radiotracer, obtained via a simple labeling procedure, exhibits favorable radiochemical purity, stability, and pharmacokinetic properties. Subsequently, cellular uptake experiments have demonstrated that <sup>68</sup>Ga-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 <sup>68</sup>Ga-DOTA-CTB holds substantial potential as a novel PET/MR imaging tracer for ALK-positive tumors.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"209 ","pages":"Article 107087"},"PeriodicalIF":4.3000,"publicationDate":"2025-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Development and preclinical evaluation of a gallium-68 labeled novel diagnostic tracer for visualizing ALK expression in tumor\",\"authors\":\"Zhen-Peng Yu , Ke-Xin Sun , Dan Zhang , Zhi-Qiang Yu , Deng-Yun Chen , Hong Zhu , Hongwei Si , Peng-Fei Dai\",\"doi\":\"10.1016/j.ejps.2025.107087\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>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 <sup>68</sup>Ga-DOTA-CTB (<sup>68</sup>Ga labeled ceritinib) based on ceritinib scaffold to monitor the ALK expression levels during targeted therapy with ceritinib. The <sup>68</sup>Ga-DOTA-CTB radiotracer, obtained via a simple labeling procedure, exhibits favorable radiochemical purity, stability, and pharmacokinetic properties. Subsequently, cellular uptake experiments have demonstrated that <sup>68</sup>Ga-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 <sup>68</sup>Ga-DOTA-CTB holds substantial potential as a novel PET/MR imaging tracer for ALK-positive tumors.</div></div>\",\"PeriodicalId\":12018,\"journal\":{\"name\":\"European Journal of Pharmaceutical Sciences\",\"volume\":\"209 \",\"pages\":\"Article 107087\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-03-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"European Journal of Pharmaceutical Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0928098725000867\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Pharmaceutical Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0928098725000867","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Development and preclinical evaluation of a gallium-68 labeled novel diagnostic tracer for visualizing ALK expression in tumor
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.
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.