Abstract
Specific targeting of radionuclides is a promising approach to improve diagnosis and treatment of tumors. Targeting vectors may be monoclonal antibodies directed toward tumour-specific antigens or regulatory peptides binding to receptors overexpressed on or by malignant cells. Depending on the aim of the procedure and the biokinetics of the targeting vectors, radionuclides with different nuclear properties (decay scheme, half-life, etc.) must be applied. Halogen radioisotopes are attractive since they exhibit a variety of nuclear properties suitable for various applications. At the same time, their chemistry shows great similarities, which enables the use of similar labelling procedures for different nuclides. A problem in using radiohalogens for labelling of tumour-targeting proteins and peptides is that the commonly used radiohalogenation methods provide labels, which, after internalisation and lysosomal digestion, rapidly “leak” from malignant cells as radiohalogenated degradation products. The main reason for such leakage is free diffusion of the radiometabolites through lysosomal and cellular membranes. This review describes current approaches in molecular design to improve cellular retention of radiohalogen labels. These approaches include the use of prosthetic groups for the attachment of radiohalogens to targeting vectors of bulky hydrophilic non-charged molecules, molecules positively charged at lysosomal pH and negatively charged molecules. The emphasis in this paper is on labelling chemistry and the results of the biological testing of labelled compounds.
Keywords: indirect radiohalogenation of proteins, radiobromine, radioiodine, astatine, tumor targeting, radioimmonotherapy, radioimmunodiagnosis, polyhedral boron anions
Current Medicinal Chemistry
Title: Approaches to Improve Cellular Retention of Radiohalogen Labels Delivered by Internalising Tumour-Targeting Proteins and Peptides
Volume: 10 Issue: 22
Author(s): V. Tolmachev, A. Orlova and H. Lundqvist
Affiliation:
Keywords: indirect radiohalogenation of proteins, radiobromine, radioiodine, astatine, tumor targeting, radioimmonotherapy, radioimmunodiagnosis, polyhedral boron anions
Abstract: Specific targeting of radionuclides is a promising approach to improve diagnosis and treatment of tumors. Targeting vectors may be monoclonal antibodies directed toward tumour-specific antigens or regulatory peptides binding to receptors overexpressed on or by malignant cells. Depending on the aim of the procedure and the biokinetics of the targeting vectors, radionuclides with different nuclear properties (decay scheme, half-life, etc.) must be applied. Halogen radioisotopes are attractive since they exhibit a variety of nuclear properties suitable for various applications. At the same time, their chemistry shows great similarities, which enables the use of similar labelling procedures for different nuclides. A problem in using radiohalogens for labelling of tumour-targeting proteins and peptides is that the commonly used radiohalogenation methods provide labels, which, after internalisation and lysosomal digestion, rapidly “leak” from malignant cells as radiohalogenated degradation products. The main reason for such leakage is free diffusion of the radiometabolites through lysosomal and cellular membranes. This review describes current approaches in molecular design to improve cellular retention of radiohalogen labels. These approaches include the use of prosthetic groups for the attachment of radiohalogens to targeting vectors of bulky hydrophilic non-charged molecules, molecules positively charged at lysosomal pH and negatively charged molecules. The emphasis in this paper is on labelling chemistry and the results of the biological testing of labelled compounds.
Export Options
About this article
Cite this article as:
Tolmachev V., Orlova A. and Lundqvist H., Approaches to Improve Cellular Retention of Radiohalogen Labels Delivered by Internalising Tumour-Targeting Proteins and Peptides, Current Medicinal Chemistry 2003; 10 (22) . https://dx.doi.org/10.2174/0929867033456666
DOI https://dx.doi.org/10.2174/0929867033456666 |
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
-
Glioblastoma Tumor Initiating Cells: Therapeutic Strategies Targeting Apoptosis and MicroRNA Pathways
Current Molecular Medicine Potentials of ES Cell Therapy in Neurodegenerative Diseases
Current Pharmaceutical Design P53 Family: At the Crossroads in Cancer Therapy
Current Medicinal Chemistry Versatility of Cancer Associated Fibroblasts: Commendable Targets for Anti-tumor Therapy
Current Drug Targets Inhibitors of Chronically Active Ras: Potential for Treatment of Human Malignancies
Recent Patents on Anti-Cancer Drug Discovery Ex Vivo Gene Transfer for Improvement of Transplanted Pancreatic Islet Viability and Function
Current Pharmaceutical Design Focus on the Use of Resveratrol as an Adjuvant in Glioblastoma Therapy
Current Pharmaceutical Design Synthesis and Preliminary Evaluation of 5-[18F]fluoroleucine
Current Radiopharmaceuticals Recent Progress in the Development of Anticancer Agents
Current Medicinal Chemistry - Anti-Cancer Agents The Emerging Role of EMT-related lncRNAs in Therapy Resistance and their Applications as Biomarkers
Current Medicinal Chemistry Targeting Never-In-Mitosis-A Related Kinase 5 in Cancer: A Review
Current Medicinal Chemistry Mouse Induced Glioma-Initiating Cell Models and Therapeutic Targets
Anti-Cancer Agents in Medicinal Chemistry The Epithelial-Mesenchymal Transition and Cancer Stem Cells: Functional and Mechanistic Links
Current Pharmaceutical Design Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer
Current Medicinal Chemistry The Neurotachykinin NK1 Receptor – A Novel Target for Diagnostics and Therapy
Current Molecular Imaging (Discontinued) MicroRNAs as Cancer Biomarkers
MicroRNA Targeting Tumor-Related Immunosuppression for Cancer Immunotherapy
Endocrine, Metabolic & Immune Disorders - Drug Targets The Metabolism of Anthocyanins
Current Drug Metabolism Microarrays and the Genetic Analysis of Brain Tumors
Current Genomics Advanced Neuroimaging Techniques in the Management of Glioblastoma Multiforme
Current Radiopharmaceuticals