Abstract
Targeted radiotherapy using radiolabelled meta-iodobenzylguanidine (MIBG) is a promising treatment option for bladder cancer, restricting the effects of radiotherapy to malignant cells thereby increasing efficacy and decreasing morbidity of radiotherapy. We investigated the efficacy of a combined gene therapy and targeted radiotherapy approach for bladder cancer using radiolabelled MIBG. The effectiveness of alternative radiohalogens and alternative preparations of radiolabelled MIBG for this therapeutic strategy were compared. Bladder cancer cells, EJ138, were transfected with a gene encoding the noradrenaline transporter (NAT) under the control of a tumour specific telomerase promoter, enabling them to actively take up radiolabelled MIBG. This resulted in tumourspecific cell kill. Uptake and retention of radioactivity in cells transfected with the NAT gene were compared with that obtained in cells transfected with the sodium iodide symporter (NIS) gene. Substantially greater uptake and longer retention of radioactivity in NAT-transfected cells was observed. Carrier-added (c.a.) [131I]MIBG, no-carrier added (n.c.a.) [131I]MIBG, and [211At]-labelled benzylguanidine (i.e. [211At] meta-astatobenzylguanidine (MABG)) were compared with respect to efficiency of induction of cell kill. N.c.a[131I]MIBG was more cytotoxic than c.a.[131I]MIBG. However, the α- emitter [211At]MABG was, by three orders of magnitude, more effective in causing tumour cell kill than the β-emitter [131I]MIBG. We conclude that NAT gene transfer combined with the administration of n.c.a.[131I]MIBG or [211At]MABG, is a promising novel treatment approach for bladder cancer therapy.
Keywords: bladder cancer, gene therapy, nat, nis, [131I]mibg, [211at]mabg
Medicinal Chemistry
Title: Comparison of Radiohaloanalogues of Meta-Iodobenzylguanidine (MIBG) for a Combined Gene- and Targeted Radiotherapy Approach to Bladder Carcinoma
Volume: 1 Issue: 6
Author(s): N. E. Fullerton, M. Boyd, S. C. Ross, S. L. Pimlott, J. Babich, D. Kirk, M. R. Zalutsky and R. J. Mairs
Affiliation:
Keywords: bladder cancer, gene therapy, nat, nis, [131I]mibg, [211at]mabg
Abstract: Targeted radiotherapy using radiolabelled meta-iodobenzylguanidine (MIBG) is a promising treatment option for bladder cancer, restricting the effects of radiotherapy to malignant cells thereby increasing efficacy and decreasing morbidity of radiotherapy. We investigated the efficacy of a combined gene therapy and targeted radiotherapy approach for bladder cancer using radiolabelled MIBG. The effectiveness of alternative radiohalogens and alternative preparations of radiolabelled MIBG for this therapeutic strategy were compared. Bladder cancer cells, EJ138, were transfected with a gene encoding the noradrenaline transporter (NAT) under the control of a tumour specific telomerase promoter, enabling them to actively take up radiolabelled MIBG. This resulted in tumourspecific cell kill. Uptake and retention of radioactivity in cells transfected with the NAT gene were compared with that obtained in cells transfected with the sodium iodide symporter (NIS) gene. Substantially greater uptake and longer retention of radioactivity in NAT-transfected cells was observed. Carrier-added (c.a.) [131I]MIBG, no-carrier added (n.c.a.) [131I]MIBG, and [211At]-labelled benzylguanidine (i.e. [211At] meta-astatobenzylguanidine (MABG)) were compared with respect to efficiency of induction of cell kill. N.c.a[131I]MIBG was more cytotoxic than c.a.[131I]MIBG. However, the α- emitter [211At]MABG was, by three orders of magnitude, more effective in causing tumour cell kill than the β-emitter [131I]MIBG. We conclude that NAT gene transfer combined with the administration of n.c.a.[131I]MIBG or [211At]MABG, is a promising novel treatment approach for bladder cancer therapy.
Export Options
About this article
Cite this article as:
Fullerton E. N., Boyd M., Ross C. S., Pimlott L. S., Babich J., Kirk D., Zalutsky R. M. and Mairs J. R., Comparison of Radiohaloanalogues of Meta-Iodobenzylguanidine (MIBG) for a Combined Gene- and Targeted Radiotherapy Approach to Bladder Carcinoma, Medicinal Chemistry 2005; 1 (6) . https://dx.doi.org/10.2174/157340605774598090
DOI https://dx.doi.org/10.2174/157340605774598090 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
Related Articles
-
HPV Pathway Profiling: HPV Related Cervical Dysplasia and Carcinoma Studies
Current Pharmaceutical Design Detection and Specific Targeting of Hypoxic Regions within Solid Tumors: Current Preclinical and Clinical Strategies
Current Medicinal Chemistry Dendrimers and Dendritic Polymers as Anti-infective Agents: New Antimicrobial Strategies for Therapeutic Drugs
Anti-Infective Agents in Medicinal Chemistry The Role of XRCC4 in Carcinogenesis and Anticancer Drug Discovery
Recent Patents on Anti-Cancer Drug Discovery Evolutioninthe Pharmacogenetics and Pharmacogenomics of Inflammatory Bowel Disease - Order Slowly Rises from the Chaos
Current Pharmacogenomics Marine Derived Anticancer Drugs Targeting Microtubule
Recent Patents on Anti-Cancer Drug Discovery Wet-lab Tested MicroRNA Assays for qPCR Studies with SYBR<sup>®</sup> Green and DNA Primers in Pig Tissues
MicroRNA Metabolomic Heterogeneity of Urogenital Tract Cancers Analyzed by Complementary Chromatographic Techniques Coupled with Mass Spectrometry
Current Medicinal Chemistry Further Vitamin D Analogs
Current Vascular Pharmacology Mechanisms of Action of DNA-Damaging Anticancer Drugs in Treatment of Carcinomas: Is Acute Apoptosis an “Off-Target” Effect?
Mini-Reviews in Medicinal Chemistry Novel Patents and Cancer Therapies for Transforming Growth Factor- Beta and Urokinase Type Plasminogen Activator: Potential Use of Their Interplay in Tumorigenesis
Recent Patents on Anti-Cancer Drug Discovery Tissue Transport of Anti-cancer Drugs
Current Pharmaceutical Design Insight View on Possible Role of Fluoroquinolones in Cancer Therapy
Current Topics in Medicinal Chemistry Toxicities of Immunosuppressive Treatment of Autoimmune Neurologic Diseases
Current Neuropharmacology Advances in Gene Therapy for Bladder Cancer
Current Gene Therapy The Coordinated Role of CYP450 Enzymes and P-gp in Determining Cancer Resistance to Chemotherapy
Current Drug Metabolism 3-Substituted Isocoumarins as Thymidine Phosphorylase Inhibitors
Letters in Drug Design & Discovery MicroRNA Polymorphisms, MicroRNA Pharmacogenomics and Cancer Susceptibility
Current Pharmacogenomics and Personalized Medicine Copper Complexes as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Anti-HER2 Treatment and Breast Cancer: State of the Art, Recent Patents, and New Strategies
Recent Patents on Anti-Cancer Drug Discovery