摘要
背景:在20世纪60年代和70年代作为抗病毒药开发的胸苷类似物2''-脱氧-2''-氟-5-甲基-1-β-D-阿拉伯呋喃糖尿嘧啶(FMAU)被翻译成临床应用于治疗单纯疱疹病毒感染。然而在FMAU的I期临床试验中,患者在药理剂量时出现神经毒性,FMAU从试验中撤出。最近,FMAU已被开发为正电子发射断层扫描(PET)成像示踪剂,通过其与癌症细胞中上调的人胸苷激酶结合来早期检测癌症。用11C或18F放射性标记的FMAU已被检查用于肿瘤细胞增殖和DNA合成的PET成像。虽然很多报道已经在FMAU上发表过一部分,但缺乏对历史发展和成像探针的系统评价。这篇综述主要集中在激酶的鉴定,FAMU的化学及其在癌症诊断和治疗评估中的应用。 目的:本研究的目的是回顾FMAU的历史发展,从其合成开发和抗病毒活性研究到其放射性标记,并将其评估为PET成像探针,用于早期发现癌症和评估治疗反应,包括已发表的报告关于18F-FMAU的临床应用。 结论:虽然FMAU作为抗病毒药物并不成功,但18F-FMAU是一种合适的放射性示踪剂,可用于早期发现癌症并评估PET治疗反应。临床级18F-FMAU生产过程需要进一步改进。 18F-FMAU具有很高的临床应用潜力,但需要进一步广泛的研究来确定这种示踪剂在诊断各种癌症和评估它们对治疗的反应。
关键词: 抗病毒剂,PET,C-11,F-18,核苷,分子成像,DNA合成。
Current Medicinal Chemistry
Title:Journey of 2′-deoxy-2′-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU): from Antiviral Drug to PET Imaging Agent
Volume: 25 Issue: 16
关键词: 抗病毒剂,PET,C-11,F-18,核苷,分子成像,DNA合成。
摘要: Background: Developed as an antiviral drug in the 1960s and 1970s, the thymidine analogue 2′-deoxy-2′-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU) was translated to clinical application for treatment of herpes simplex virus infection. In phase I clinical trial of FMAU; however, patients experienced neurotoxicity at the pharmacological dose, and FMAU was withdrawn from the trial. More recently, FMAU has been developed as a tracer for positron emission tomography (PET) imaging in early detection of cancer through its binding to human thymidine kinase, which is upregulated in cancer cells. FMAU radiolabeled with 11C or 18F has been examined for PET imaging of tumor cell proliferation and DNA synthesis. Although many reports have been partially published on FMAU, systematic reviews outlining the historic development and imaging probe are lacking. This review is focused on the identification of kinases, the chemistry of FAMU and its application in cancer diagnosis and therapy assessment.
Objective: The aim of this study was to review the historic development of FMAU, from its synthetic development and antiviral activity studies to its radiolabeling and evaluate it as a PET imaging probe for the early detection of cancer and assessment of treatment response, including published reports on the clinical utility of 18F-FMAU.
Conclusion: While FMAU was not successful as an antiviral agent, 18F-FMAU is a suitable radiotracer for early detection of cancer and assessment of response to therapy by PET. The process of clinical grade 18F-FMAU production requires further improvement. 18F-FMAU has high potential for clinical application, but further extensive studies are needed to establish this tracer in the diagnosis of various cancers and assessment of their response to therapy.
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Journey of 2′-deoxy-2′-fluoro-5-methyl-1-β-D-arabinofuranosyluracil (FMAU): from Antiviral Drug to PET Imaging Agent, Current Medicinal Chemistry 2018; 25 (16) . https://dx.doi.org/10.2174/0929867325666171129125217
DOI https://dx.doi.org/10.2174/0929867325666171129125217 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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