P-glycoprotein is a protective efflux transporter at the blood-brain barrier showing altered function in many neurological disorders. The purpose of this study was to validate [F]MC225 as a radiotracer for measuring P-glycoprotein function with positron emission tomography. Three groups of Sprague-Dawley rats were used to assess tracer uptake at baseline (group 1), after inhibition of P-glycoprotein (group 2), and after inhibition of both P-glycoprotein and breast cancer resistance protein (Bcrp, group 3). A two-tissue compartment model with a metabolite-corrected plasma input function provided the best fit to the positron emission tomography data, but parameter estimates were more reliable in a one-tissue compartment model, which was selected as the preferred model. Regional distribution volumes ( V) in the control group ranged from 6 to 11, which is higher than for other radiotracers. [F]MC225 showed transporter selectivity, since inhibition of P-glycoprotein caused a two to fourfold increase in the cerebral V values, but additional inhibition of Bcrp did not cause any further increase. Metabolic stability of [F]MC225 was moderate (at 1 h post-injection 15% of plasma radioactivity and 76% of brain radioactivity represented intact parent). Thus, [F]MC225 may be a useful radiotracer to measure especially increases of P-glycoprotein function at the blood-brain barrier.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453451 | PMC |
| http://dx.doi.org/10.1177/0271678X16654493 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Regarding flotillin knockdown, drug resistance is reversed in colorectal cancer (CRC) cell lines; this is associated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway, as our previous experimental results indicated. However, the exact mechanism underlying this pathway remains unclear. PI3K inhibitor and activator were added separately to clarify the role of the PI3K pathway in reversing drug resistance.
View Article and Find Full Text PDFStudy on the absorption characteristics of euscaphic acid and tiliroside in fruits of Retz.
PeerJ
January 2025
Chinese University of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, China.
The fruits of Retz. (FRL) have a long history of medicinal use, known for their rich composition of flavonoids, polyphenols, amino acids, sugars, and other bioactive compounds. FRL exhibits pharmacological effects such as antioxidant, antiviral, antibacterial, and antitumor activities, making it a valuable resource with significant development potential in both the food and pharmaceutical industries.
View Article and Find Full Text PDFCo-administration of Rifampicin and Boswellia Serrata Mitigates Testicular Toxicity Caused by Aflatoxin B1.
Toxicon
January 2025
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Firat University, Elazig, Turkey.
The current study was aimed to investigate the effect of rifampicin (Rif), a stimulator of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), on limiting the passage of AFB1 (Aflatoxin B1) into testicular tissue. The second objective was to examine the potential protective effects of Boswellia serrata extract (BSE), which exhibits a strong antioxidant capacity, alone or incombination with Rif against testicular damage induced by AFB1. A total of 49 male Sprague-Dawley rats were randomly divided into seven experimental groups as follows: control (placebo), Rif (10 mg/kg), BSE (500 mg/kg), AFB1 (0.
View Article and Find Full Text PDFSystematic review of amyloid-beta clearance proteins from the brain to the periphery: implications for Alzheimer's disease diagnosis and therapeutic targets.
Neural Regen Res
January 2025
Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China Medical University, Shenyang, Liaoning Province, China.
Amyloid-beta clearance plays a key role In the pathogenesis of Alzheimer's disease. However, the variation in functional proteins involved in amyloid-beta clearance and their correlation with amyloid-beta levels remain unclear. In this study, we conducted meta-analyses and a systematic review using studies from the PubMed, Embase, Web of Science, and Cochrane Library databases, including journal articles published from inception to June 30, 2023.
View Article and Find Full Text PDFOral Administration of [F]MC225 for Quantification of P-glycoprotein Function: A Feasibility Study.
Mol Imaging Biol
January 2025
Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Purpose: This preclinical study explored the feasibility of assessing P-glycoprotein (P-gp) function in both brain and gastrointestinal (GI) tract of rats using positron emission tomography (PET) following oral administration of [F]MC225. Different oral administration protocols were evaluated, and radioactivity uptake was compared with uptake following intravenous administration.
Procedures: Twelve male Wistar rats were divided into four groups and subjected to intravenous or oral [F]MC225 administration protocols: G (intravenous route), G (oral administration without fasting), G (oral administration with fasting), and G (oral administration with fasting following administration of the P-gp inhibitor tariquidar).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!