Abstract
P-glycoprotein function is associated with a number of neurodegenerative and psychiatric diseases as well as with pharmacoresistance to for example antiepileptic drugs. The ability to measure P-gp function in vivo would allow for an increased understanding of the mechanisms of disease and treatment. This review assesses the various approaches to in vivo quantification of P-gp function using currently available P-gp tracers and PET in humans. First, the use of compartment models, and their interpretation in terms of P-gp function at the blood-brain barrier, is discussed. Then, the methods that have been used to quantify PET data of the P-gp tracers [11C]verapamil, [11C]N-desmetyl-loperamide (dLop), [11C]laniquidar, [11C]phenytoin, [11C]tariquidar and [11C]elacridar are reviewed. In summary, the extraction of P-gp substrate PET tracers, which is their plasma to tissue rate constant K1 corrected for variations in regional cerebral blood flow, is generally considered to be the preferred measure of P-gp function.
Keywords: PET, P-glycoprotein, quantification, tracer kinetics, blood-brain barrier.
Current Pharmaceutical Design
Title:Kinetic Models for Measuring P-glycoprotein Function at the Blood-Brain Barrier with Positron Emission Tomography
Volume: 22 Issue: 38
Author(s): Mark Lubberink
Affiliation:
Keywords: PET, P-glycoprotein, quantification, tracer kinetics, blood-brain barrier.
Abstract: P-glycoprotein function is associated with a number of neurodegenerative and psychiatric diseases as well as with pharmacoresistance to for example antiepileptic drugs. The ability to measure P-gp function in vivo would allow for an increased understanding of the mechanisms of disease and treatment. This review assesses the various approaches to in vivo quantification of P-gp function using currently available P-gp tracers and PET in humans. First, the use of compartment models, and their interpretation in terms of P-gp function at the blood-brain barrier, is discussed. Then, the methods that have been used to quantify PET data of the P-gp tracers [11C]verapamil, [11C]N-desmetyl-loperamide (dLop), [11C]laniquidar, [11C]phenytoin, [11C]tariquidar and [11C]elacridar are reviewed. In summary, the extraction of P-gp substrate PET tracers, which is their plasma to tissue rate constant K1 corrected for variations in regional cerebral blood flow, is generally considered to be the preferred measure of P-gp function.
Export Options
About this article
Cite this article as:
Lubberink Mark, Kinetic Models for Measuring P-glycoprotein Function at the Blood-Brain Barrier with Positron Emission Tomography, Current Pharmaceutical Design 2016; 22 (38) . https://dx.doi.org/10.2174/1381612822666160804093852
DOI https://dx.doi.org/10.2174/1381612822666160804093852 |
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
-
Small Peptide and Protein-based Molecular Probes for Imaging Neurological Diseases
Current Protein & Peptide Science Basis for the Application of Analytical Models of the Bloch NMR Flow Equations for Functional Magnetic Resonance Imaging (fMRI): A Review
Recent Patents on Medical Imaging Understanding Effects of Psychological Stress on Physiology and Disease Through Human Stressome - An Integral Algorithm
Current Bioinformatics Epilepsy and Neurosurgery: Historical Highlights
Current Pharmaceutical Design Structure-Activity Relationships of Selective GABA Uptake Inhibitors
Current Topics in Medicinal Chemistry Neurological Aspects of Medical Use of Cannabidiol
CNS & Neurological Disorders - Drug Targets Catatonia: A Brief Update
Current Psychiatry Reviews Patient’s Perceptions of the Cannabis-psychosis Link - A Systematic Review
Current Pharmaceutical Design Valproic Acid and the Liver Injury in Patients with Epilepsy: An Update
Current Pharmaceutical Design Is There a Relationship Between Sweet Taste and Seizures? Anticonvulsant and Proconvulsant Effects of Non-Nutritive Sweeteners
Combinatorial Chemistry & High Throughput Screening 3D QSAR Studies on 1, 3, 4-Thiadiazole Derivatives: An Approach to Design Novel Anticonvulsants
Medicinal Chemistry Metabotropic Glutamate Receptor 7: From Synaptic Function to Therapeutic Implications
Current Neuropharmacology Alzheimer’s Disease Genetic Risk Factor APOE-ε4 Also Affects Normal Brain Function
Current Alzheimer Research Repetitive Transcranial Magnetic Stimulation for ALS
CNS & Neurological Disorders - Drug Targets QSAR Studies for the Pharmacological Inhibition of Glycogen Synthase Kinase-3
Medicinal Chemistry Evaluating Drug Safety in Children and Adolescents with Bipolar Disorder
Current Drug Safety Assessment of Possible Drug Interactions in Patients with Psoriasis and Associated Comorbid Medical Conditions: An Observational Study
Reviews on Recent Clinical Trials The Orexin System: A Potential Player in the Pathophysiology of Absence Epilepsy
Current Neuropharmacology Therapeutic Targets for the Management of Peripheral Nerve Injury- Induced Neuropathic Pain
CNS & Neurological Disorders - Drug Targets Predicting Targeted Polypharmacology for Drug Repositioning and Multi- Target Drug Discovery
Current Medicinal Chemistry