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
-
Intersection of MicroRNA and Gene Regulatory Networks and their Implication in Cancer
Current Pharmaceutical Biotechnology Diagnostic Imaging of Hepatocellular Carcinoma - A Pictorial Essay
Current Medical Imaging Evolution and Pathogenesis of Oncoviruses Associated with Head and Neck Cancer: History and Current Concepts
Recent Patents on Biomarkers Heat Shock Protein Inhibitors for the Treatment of Fungal Infections
Recent Patents on Anti-Infective Drug Discovery Identification of Molecular Targets Associated with Ethanol Toxicity and Implications in Drug Development
Current Pharmaceutical Design Manipulation of the Immune System for Cancer Defeat: A Focus on the T Cell Inhibitory Checkpoint Molecules
Current Medicinal Chemistry Epigenetic Regulation of Epithelial to Mesenchymal Transition
Current Cancer Drug Targets Quinoxalinone as a Privileged Platform in Drug Development
Mini-Reviews in Medicinal Chemistry Medical devices regulatory aspects: a special focus on polymeric material based devices
Current Pharmaceutical Design Cucurbitacin IIb from Ibervillea sonorae Induces Apoptosis and Cell Cycle Arrest via STAT3 Inhibition
Anti-Cancer Agents in Medicinal Chemistry Resveratrol as a Chemopreventive Agent: A Promising Molecule for Fighting Cancer
Current Drug Targets Implications of Melatonin Therapy in Irritable Bowel Syndrome: A Systematic Review
Current Pharmaceutical Design Molecular Targets of Omega-3 Fatty Acids for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry NMR-based Metabolite Profiling of Pancreatic Cancer
Current Metabolomics Melatonin, a Potential Therapeutic Agent for Smooth Muscle-Related Pathological Conditions and Aging
Current Medicinal Chemistry EGFR High Expression, but not KRAS Status, Predicts Sensitivity of Pancreatic Cancer Cells to Nimotuzumab Treatment In Vivo
Current Cancer Drug Targets Iron Oxide Nanoparticle-induced Oxidative Stress and Genotoxicity in Human Skin Epithelial and Lung Epithelial Cell Lines
Current Pharmaceutical Design Genistein Aglycone: A Dual Mode of Action Anti-Osteoporotic Soy Isoflavone Rebalancing Bone Turnover Towards Bone Formation
Current Medicinal Chemistry Monoclonal Antibodies in Rare Acquired Thrombotic Disorders: The Paradigms of Paroxysmal Nocturnal Hemoglobinuria, Thrombotic Thrombocytopenic Purpura and Central Retinal Vein Occlusion
Current Vascular Pharmacology Comprehensive Profiling of the Low Molecular Weight Proteins and Peptides in Weak Cation Exchange Beads Human Serum Retentate
Protein & Peptide Letters