Abstract
Human thymidine kinase (TK1) is a key enzyme that is up-regulated in cancer cells and phosphorylates thymidine and some of its analogs to their monophosphates. The monophosphates are converted to their di- and triphosphates by the nucleoside kinases, and some of these nucleoside triphosphates are incorporated into DNA by DNA polymerase. The nucleoside analogs are transported into cells by concentrative nucleoside transporter or equilibrative nucleoside transporter. Given the unique property of TK1 and the nucleoside transporter systems, thymidine and its analogs have been radiolabeled for positron emission tomography (PET) imaging of tumor proliferation and DNA synthesis. Because thymidine is catabolized in vivo by thymidine phosphorylase, radiolabeled thymidine has not been successful in PET imaging of tumor proliferation. However, some of its analogs have been radiolabeled and successfully used in PET imaging of cell proliferation as well as DNA synthesis. Much work has been done in synthesis, radiosynthesis, and biological evaluation of these analogs for PET imaging of tumor proliferation. We review the chemistry, radiochemistry, and biological studies published to date, including structure activity relationship and PET imaging of the radiolabeled thymidine analogs. Information on radiolabeling and PET imaging with various nucleoside analogs is presented.
Keywords: PET, F-18, Nucleoside, Molecular Imaging, DNA synthesis
Current Medicinal Chemistry
Title: Pyrimidine Nucleosides in Molecular PET Imaging of Tumor Proliferation
Volume: 17 Issue: 11
Author(s): M. M. Alauddin and J. G. Gelovani
Affiliation:
Keywords: PET, F-18, Nucleoside, Molecular Imaging, DNA synthesis
Abstract: Human thymidine kinase (TK1) is a key enzyme that is up-regulated in cancer cells and phosphorylates thymidine and some of its analogs to their monophosphates. The monophosphates are converted to their di- and triphosphates by the nucleoside kinases, and some of these nucleoside triphosphates are incorporated into DNA by DNA polymerase. The nucleoside analogs are transported into cells by concentrative nucleoside transporter or equilibrative nucleoside transporter. Given the unique property of TK1 and the nucleoside transporter systems, thymidine and its analogs have been radiolabeled for positron emission tomography (PET) imaging of tumor proliferation and DNA synthesis. Because thymidine is catabolized in vivo by thymidine phosphorylase, radiolabeled thymidine has not been successful in PET imaging of tumor proliferation. However, some of its analogs have been radiolabeled and successfully used in PET imaging of cell proliferation as well as DNA synthesis. Much work has been done in synthesis, radiosynthesis, and biological evaluation of these analogs for PET imaging of tumor proliferation. We review the chemistry, radiochemistry, and biological studies published to date, including structure activity relationship and PET imaging of the radiolabeled thymidine analogs. Information on radiolabeling and PET imaging with various nucleoside analogs is presented.
Export Options
About this article
Cite this article as:
Alauddin M. M. and Gelovani G. J., Pyrimidine Nucleosides in Molecular PET Imaging of Tumor Proliferation, Current Medicinal Chemistry 2010; 17 (11) . https://dx.doi.org/10.2174/092986710790820606
DOI https://dx.doi.org/10.2174/092986710790820606 |
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
-
Metals and Metal Derivatives in Medicine
Mini-Reviews in Medicinal Chemistry Quinoxalinone as a Privileged Platform in Drug Development
Mini-Reviews in Medicinal Chemistry Survivin: Role in Normal Cells and in Pathological Conditions
Current Cancer Drug Targets Functions of Polo-Like Kinases: A Journey From Yeast To Humans
Protein & Peptide Letters Photothermal Therapy: A New Approach to Eradicate Cancer
Current Nanoscience Fungal Biofilm – A Real Obstacle Against an Efficient Therapy: Lessons from Candida
Current Topics in Medicinal Chemistry Targeting Telomerase for Cancer Therapy
Current Cancer Therapy Reviews Anti-Tumor Vaccines in Head and Neck Cancer: Targeting Immune Responses to the Tumor
Current Cancer Drug Targets Evaluation of the Risk/Benefit Ratio of Old and New Anti-Inflammatory Drugs
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Anticancer Actions of Omega-3 Fatty Acids - Current State and Future Perspectives
Anti-Cancer Agents in Medicinal Chemistry Nanosponges Encapsulated Phytochemicals for Targeting Cancer: A Review
Current Drug Targets Long Non-coding RNA AFAP1-AS1 Facilitates Prostate Cancer Progression by Regulating miR-15b/IGF1R Axis
Current Pharmaceutical Design Research on Gastric Cancer’s Drug-resistant Gene Regulatory Network Model
Current Bioinformatics New Insights into Binding Interfaces of Coagulation Factors V and VIII and their Homologues - Lessons from High Resolution Crystal Structures
Current Protein & Peptide Science Radioprotective Gene Therapy
Current Gene Therapy Telomeres, Telomerase and Malignant Transformation
Current Molecular Medicine Inhibitory Potential of Dietary Nutraceuticals on Cellular PI3K/Akt Signaling: Implications in Cancer Prevention and Therapy
Current Topics in Medicinal Chemistry The Functional Role of Long Non-coding RNA UCA1 in Human Multiple Cancers: a Review Study
Current Molecular Medicine Processed Foods, Dysbiosis, Systemic Inflammation, and Poor Health
Current Nutrition & Food Science Annexin A5 Imaging: An Academic Research – Clinical Trials and Theses
Current Molecular Imaging (Discontinued)