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
-
Feasibility of a Scale-down Production of [<sup>68</sup>Ga]Ga-NODAGA-Exendin-4
in a Hospital Based Radiopharmacy
Current Radiopharmaceuticals Iron Oxide Nanoparticle-induced Oxidative Stress and Genotoxicity in Human Skin Epithelial and Lung Epithelial Cell Lines
Current Pharmaceutical Design Development of personalized molecular therapy for acute myeloid leukemia
Current Pharmaceutical Biotechnology Noble metal-dithiocarbamates precious allies in the fight against cancer
Mini-Reviews in Medicinal Chemistry Synthesis and Biological Activity of Chiral Dihydropyrazole: Potential Lead for Drug Design
Mini-Reviews in Medicinal Chemistry Alterations in Homocysteine Metabolism Among Alcohol Dependent Patients - Clinical, Pathobiochemical and Genetic Aspects
Current Drug Abuse Reviews Oxidative Stress and Cellular Senescence: The Key Tumor-promoting Factors in Colon Cancer and Beneficial Effects of Polyphenols in Colon Cancer Prevention
Current Cancer Therapy Reviews Exploiting Significance of Physical Exercise in Prevention of Gastrointestinal Disorders
Current Pharmaceutical Design Hepatoma-Derived Growth Factor in Carcinogenesis and Cancer Progression
Current Drug Therapy Src Family Kinases in the Central Nervous System: Their Emerging Role in Pathophysiology of Migraine and Neuropathic Pain
Current Neuropharmacology Microaspiration in Intubated Critically Ill Patients: Diagnosis and Prevention
Infectious Disorders - Drug Targets A Multi-targeted Natural Flavonoid Myricetin Suppresses Lamellipodia and Focal Adhesions Formation and Impedes Glioblastoma Cell Invasiveness and Abnormal Motility
CNS & Neurological Disorders - Drug Targets Mesothelioma - Update on Management
Current Respiratory Medicine Reviews The Diagnostic Utility of Pleural Fluid Tests in Clinical Practice
Current Respiratory Medicine Reviews Peripheral TRPV1 Receptors As Targets for Drug Development: New Molecules and Mechanisms
Current Pharmaceutical Design Unequivocal Role of Pyrazine Ring in Medicinally Important Compounds: A Review
Mini-Reviews in Medicinal Chemistry Function of miRNA in Controlling Drug Resistance of Human Cancers
Current Drug Targets Interactions of the Aryl Hydrocarbon Receptor with Inflammatory Mediators:Beyond CYP1A Regulation
Current Drug Metabolism Pharmacokinetic Interactions Between Herbal Medicines and Prescribed Drugs: Focus on Drug Metabolic Enzymes and Transporters
Current Drug Metabolism Towards Understanding the Role of Cancer-Associated Inflammation in Chemoresistance
Current Pharmaceutical Design