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phase I clinical trial of FMAU; however, patients experienced neurotoxicity at the pharmacological dose, and FMAU was withdrawn from the trial.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
-
Passive and Active Tumour Targeting with Nanocarriers
Current Drug Discovery Technologies Molecular Modeling Applied to Anti-Cancer Drug Development
Anti-Cancer Agents in Medicinal Chemistry Acute and Chronic Stress-Induced Disturbances of Microglial Plasticity, Phenotype and Function
Current Drug Targets Phosphine-Gold(I) Compounds as Anticancer Agents: General Description and Mechanisms of Action
Anti-Cancer Agents in Medicinal Chemistry Promises of Apoptosis-Inducing Peptides in Cancer Therapeutics
Current Pharmaceutical Biotechnology Bioluminescent Proteins Prediction with Voting Strategy
Current Bioinformatics Enrichment of Up-regulated and Down-regulated Gene Clusters Using Gene Ontology, miRNAs and lncRNAs in Colorectal Cancer
Combinatorial Chemistry & High Throughput Screening The Molecular Bases of the Self-Renewal and Differentiation of Leukemic Stem Cells
Current Cancer Therapy Reviews Immunotherapy for Prostate Cancer
Current Pharmaceutical Design Increased Paternal Age and Child Health and Development
Current Pediatric Reviews Oxidative Phosphorylation as a Target to Arrest Malignant Neoplasias
Current Medicinal Chemistry Extraction, Isolation and Analysis of Chondroitin Sulfate Glycosaminoglycans
Recent Patents on Food, Nutrition & Agriculture Vascular Endothelial Growth Factor (VEGF) in the Pathogenesis of Diabetic Nephropathy of Type 1 Diabetes Mellitus
Current Drug Targets New Insight into P-Glycoprotein as a Drug Target
Anti-Cancer Agents in Medicinal Chemistry Stimuli-Responsive Nanoparticles for siRNA Delivery
Current Pharmaceutical Design HGF and RhoGTPases in Cancer Cell Motility
Current Signal Transduction Therapy Potential Health Benefits of a Pomegranate Extract, Rich in Phenolic Compounds, in Intestinal Inflammation
Current Nutrition & Food Science Epigenetic Multiple Modulators
Current Topics in Medicinal Chemistry Pleiotropic Effect of Mahanine and Girinimbine Analogs: Anticancer Mechanism and its Therapeutic Versatility
Anti-Cancer Agents in Medicinal Chemistry Steroid 5α-Reductase as a Novel Therapeutic Target for Schizophrenia and Other Neuropsychiatric Disorders
Current Pharmaceutical Design