Abstract
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phase I clinical trial of FMAU; however, patients experienced neurotoxicity at the pharmacological dose, and FMAU was withdrawn from the trial.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.
Keywords: Antiviral agent, PET, C-11, F-18, nucleoside, molecular imaging, DNA synthesis.
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
Author(s): Mian M. Alauddin*
Affiliation:
- Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX,United States
Keywords: Antiviral agent, PET, C-11, F-18, nucleoside, molecular imaging, DNA synthesis.
Abstract: 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.
Export Options
About this article
Cite this article as:
Alauddin M. Mian *, 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 |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Autoimmune Pancreatitis and Diagnostic Criteria
Current Immunology Reviews (Discontinued) In Vivo Pharmacokinetic and Tissue Distribution Studies in Mice of Alternative Formulations for Local and Systemic Delivery of Paclitaxel: Gel, Film, Prodrug, Liposomes and Micelles
Current Drug Delivery Application of Electroporation in DNA Vaccination Protocols
Current Gene Therapy New Cathepsin D Inhibitor Library Utilizing Hydroxyethyl Isosteres with Cyclic Tertiary Amines
Medicinal Chemistry Efficacy and Safety of Nilutamide in Patients with Metastatic Prostate Cancer who Underwent Orchiectomy: A Systematic Review and Metaanalysis
Current Clinical Pharmacology Structure, Biological Properties and Applications of Marine-derived Polysaccharides
Current Organic Chemistry Adenoviral Vectors for Cancer Gene Therapy
Current Genomics The Molecular Bases of the Self-Renewal and Differentiation of Leukemic Stem Cells
Current Cancer Therapy Reviews Strategies for the Preparation of Bifunctional Gadolinium(III) Chelators
Current Organic Synthesis Microbubble-Assisted p53, RB, and p130 Gene Transfer in Combination with Radiation Therapy in Prostate Cancer
Current Gene Therapy Anorexia Nervosa and the Use of Total Parenteral Nutrition Refeeding
Current Nutrition & Food Science A Role for Milk Proteins and their Peptides in Cancer Prevention
Current Pharmaceutical Design TWIST1 Gene: First Insights in Felis catus
Current Genomics MicroRNAs as Therapeutic Agents: The Future of the Battle Against Cancer
Current Topics in Medicinal Chemistry Detection of Early Cancer: Genetics or Immunology? Serum Autoantibody Profiles as Markers of Malignancy
Anti-Cancer Agents in Medicinal Chemistry The Adverse Effects of Smoking on Health Outcomes in Bipolar Disorder: A Review and Synthesis of Biological Mechanisms
Current Molecular Medicine Signal Transduction Pathway Regulated by Genistein and its Therapeutic Use
Current Signal Transduction Therapy HIV Entry Inhibitors Targeting gp41: From Polypeptides to Small-Molecule Compounds
Current Pharmaceutical Design Interlinking of Hypoxia and Estrogen in Thyroid Cancer Progression
Current Medicinal Chemistry Osthole: A Multifunctional Natural Compound with Potential Anticancer, Antioxidant and Anti-inflammatory Activities
Mini-Reviews in Medicinal Chemistry