Abstract
Chemotherapeutic treatment of cancer patients is often unsuccessful, due to the involvement of various mechanisms, leading to multidrug resistance (MDR). In this review, I describe the mechanisms involved in MDR. Furthermore, results obtained by imaging of P-glycoprotein (P-gp) and the multidrug resistance associated protein (MRP) are reviewed. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are unique techniques to study P-gp- and MRP-mediated transport. The radiopharmaceutical 99mTc-sestamibi is a substrate for both P-gp and MRP. This tracer has been used for tumor imaging in clinical studies, and to visualize blockade of P-gp mediated transport after modulation of the P-gp pump. Other 99mTcradiopharmaceuticals such as 99mTc- tetrofosmin and several 99mTc-Q-complexes are also substrates for Pgp. Until now, for these compounds only results from in vitro and animal studies are available. For quantification of P-gp mediated transport with PET in vivo, several agents, such as [11C]colchicine, [11C]verapamil and [11C]daunorubicin have been evaluated. In vivo results suggest that these radiopharmaceuticals can be used to image P-gp function in tumors. 124I and 76Br radiolabeled doxorubicin analogues are also useful to examine P-gp mediated transport. Leukotrienes are specific substrates for MRP. Therefore, N-[11C]acetyl-leukotriene E4 provides the opportunity to study MRP function non-invasively. Results obtained with this radiopharmaceutical in MRP2 mutated GY/TR- rats indicate visualization of MRP-mediated transport. This tracer enables to study MRP transport function abnormalities in vivo such as in Dubin-Johnson patients, who are MRP2 gene deficient. In conclusion, it is feasible to study the functionality of MDR transporters in vivo, both with SPECT and with PET. Such imaging techniques may become an important factor in the development of novel chemotherapeutic drugs.
Current Pharmaceutical Design
Title: Monitoring Interactions at ATP-Dependent Drug Efflux Pumps
Volume: 6 Issue: 16
Author(s): N. H. Hendrikse
Affiliation:
Abstract: Chemotherapeutic treatment of cancer patients is often unsuccessful, due to the involvement of various mechanisms, leading to multidrug resistance (MDR). In this review, I describe the mechanisms involved in MDR. Furthermore, results obtained by imaging of P-glycoprotein (P-gp) and the multidrug resistance associated protein (MRP) are reviewed. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are unique techniques to study P-gp- and MRP-mediated transport. The radiopharmaceutical 99mTc-sestamibi is a substrate for both P-gp and MRP. This tracer has been used for tumor imaging in clinical studies, and to visualize blockade of P-gp mediated transport after modulation of the P-gp pump. Other 99mTcradiopharmaceuticals such as 99mTc- tetrofosmin and several 99mTc-Q-complexes are also substrates for Pgp. Until now, for these compounds only results from in vitro and animal studies are available. For quantification of P-gp mediated transport with PET in vivo, several agents, such as [11C]colchicine, [11C]verapamil and [11C]daunorubicin have been evaluated. In vivo results suggest that these radiopharmaceuticals can be used to image P-gp function in tumors. 124I and 76Br radiolabeled doxorubicin analogues are also useful to examine P-gp mediated transport. Leukotrienes are specific substrates for MRP. Therefore, N-[11C]acetyl-leukotriene E4 provides the opportunity to study MRP function non-invasively. Results obtained with this radiopharmaceutical in MRP2 mutated GY/TR- rats indicate visualization of MRP-mediated transport. This tracer enables to study MRP transport function abnormalities in vivo such as in Dubin-Johnson patients, who are MRP2 gene deficient. In conclusion, it is feasible to study the functionality of MDR transporters in vivo, both with SPECT and with PET. Such imaging techniques may become an important factor in the development of novel chemotherapeutic drugs.
Export Options
About this article
Cite this article as:
Hendrikse H. N., Monitoring Interactions at ATP-Dependent Drug Efflux Pumps, Current Pharmaceutical Design 2000; 6 (16) . https://dx.doi.org/10.2174/1381612003398834
DOI https://dx.doi.org/10.2174/1381612003398834 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Inhibitors of Endocannabinoid Degradation as Potential Therapeutic Agents: An Update
Medicinal Chemistry Reviews - Online (Discontinued) Integrins in Pulmonary Inflammatory Diseases
Current Pharmaceutical Design Targeting Chemokines in Cancer
Current Immunology Reviews (Discontinued) Novel Peptide Mimetics Based on N-protected Amino Acids Derived from Isomannide as Potential Inhibitors of NS3 Serine Protease of Hepatitis C Virus
Letters in Organic Chemistry Graphical Abstracts:
Current Topics in Medicinal Chemistry Testosterone as Potential Effective Therapy in Treatment of Obesity in Men with Testosterone Deficiency: A Review
Current Diabetes Reviews Evolution of Reactive mPEG Polymers for the Conjugation of Peptides and Proteins
Current Organic Chemistry Limitations of Current Antiretroviral Agents and Opportunities for Development
Current Pharmaceutical Design Toll-Like Receptors and Inflammation in the CNS
Current Drug Targets - Inflammation & Allergy Direct Inhibitors of Ras-Effector Protein Interactions
Mini-Reviews in Medicinal Chemistry <i>In vitro</i> and <i>In vivo</i> Toxicity Assessment of Metallic Nanoparticulate Systems for Skin Targeting
Current Nanotoxicity and Prevention (Discontinued) An Update On Proficiency of Voltage-gated Ion Channel Blockers in the Treatment of Inflammation-associated Diseases
Current Drug Targets Evidence for Complex Binding Profiles and Species Differences at the Translocator Protein (TSPO) (18 kDa)
Current Molecular Medicine New Anticancer Drugs from Marine Cyanobacteria
Current Drug Targets Microglia NLRP3 Inflammasomes Activation Involving Diabetic Neuroinflammation in Diabetic Mice and BV2 Cells
Current Pharmaceutical Design Animal Models for Evaluation of Drug-Drug Interaction Potential of Biotherapeutics
Current Drug Metabolism Antibody Based Therapies in Acute Leukemia
Current Drug Targets Pain Alleviation in Anti-Inflammatory and Anti-Allergic Conditions
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Epitope-Driven TB Vaccine Development: A Streamlined Approach Using Immuno-Informatics, ELISpot Assays, and HLA Transgenic Mice
Current Molecular Medicine Effects of Physical Exercise on Inflammatory Markers of Atherosclerosis
Current Pharmaceutical Design