Trial reportJournal of nuclear medicine : official publication, Society of Nuclear Medicine2010
P-glycoprotein function at the blood-brain barrier in humans can be quantified with the substrate radiotracer 11C-N-desmethyl-loperamide.
Trial report in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
66 citing papers in PubMed, 131 citations in OpenAlex.
- Effect of P-glycoprotein inhibition at the blood-brain barrier on brain distribution of (R)-[British journal of clinical pharmacology · 2017Trial
- Approaching complete inhibition of P-glycoprotein at the human blood-brain barrier: an (R)-[11C]verapamil PET study.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Trial
- Increased permeability-glycoprotein inhibition at the human blood-brain barrier can be safely achieved by performing PET during peak plasma concentrations of tariquidar.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2015Trial
- Pharmacokinetics of single ascending doses of the P-glycoprotein inhibitor tariquidar in healthy subjects.Pharmacology · 2013Trial
- Designing a Small Molecule for PET Radiotracing: [Molecules (Basel, Switzerland) · 2025Review
- Beyond the Walls of Troy: A Scoping Review on Pharmacological Strategies to Enhance Drug Delivery Across the Blood-Brain Barrier and Blood-Tumor Barrier.International journal of molecular sciences · 2025Article
- Hypoxia tolerance determine differential gelsenicine-induced neurotoxicity between pig and mouse.BMC medicine · 2025Article
- Do P-glycoprotein-mediated drug-drug interactions at the blood-brain barrier impact morphine brain distribution?Journal of pharmacokinetics and pharmacodynamics · 2025Article
- [Fluids and barriers of the CNS · 2024Article
- ATP-binding cassette transporter inhibitor potency and substrate drug affinity are critical determinants of successful drug delivery enhancement to the brain.Fluids and barriers of the CNS · 2024Article
- St. John's wort extract with a high hyperforin content does not induce P-glycoprotein activity at the human blood-brain barrier.Clinical and translational science · 2024Article
- Performance and Sensitivity of [Molecular pharmaceutics · 2024Article
- [Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Article
- Parametric Imaging of P-Glycoprotein Function at the Blood-Brain Barrier Using kMolecular imaging and biology · 2023Article
- Research progress on the regulation and mechanism of borneol on the blood-brain barrier in pathological states: a narrative review focused on ischemic stroke and cerebral glioma.Translational cancer research · 2023Review
- P-glycoprotein: new insights into structure, physiological function, regulation and alterations in disease.Heliyon · 2022Review
- Discovery and development of brain-penetrantActa pharmaceutica Sinica. B · 2022Article
- In Vivo Studies of Drug BBB Transport: Translational Challenges and the Role of Brain Imaging.Handbook of experimental pharmacology · 2022Article
- Comparative vulnerability of PET radioligands to partial inhibition of P-glycoprotein at the blood-brain barrier: A criterion of choice?Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Successful Prediction of Human Steady-State Unbound Brain-to-Plasma Concentration Ratio of P-gp Substrates Using the Proteomics-Informed Relative Expression Factor Approach.Clinical pharmacology and therapeutics · 2021Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledPermeability-glycoprotein (P-gp), an efflux transporter in several organs, acts at the blood-brain barrier to protect the brain from exogenous toxins. P-gp almost completely blocks brain entry of the PET radiotracer (11)C-N-desmethyl-loperamide ((11)C-dLop). We examined the ability of (11)C-dLop to quantify P-gp function in humans after increasing doses of tariquidar, an inhibitor of P-gp.
methodsSeventeen healthy volunteers had a total of 23 PET scans with (11)C-dLop at baseline and after increasing doses of tariquidar (2, 4, and 6 mg/kg intravenously). A subset of subjects received PET with (15)O-H(2)O to measure cerebral blood flow. Brain uptake of (11)C-dLop was quantified in 2 ways. Without blood data, uptake was measured as area under the time-activity curve in the brain from 10 to 30 min (AUC(10-30)). With arterial blood data, brain uptake was quantified with compartmental modeling to estimate the rates of entry into (K(1)) and efflux from (k(2)) the brain.
resultsBrain uptake of radioactivity was negligible at baseline and increased only slightly (approximately 30%) after 2 mg of tariquidar per kilogram. In contrast, 4 and 6 mg of tariquidar per kilogram increased brain uptake 2- and 4-fold, respectively. Greater brain uptake reflected greater brain entry (K(1)), because efflux (k(2)) and cerebral blood flow did not differ between tariquidar-treated and untreated subjects. In the subjects who received the highest dose of tariquidar (and had the highest brain uptake), regional values of K(1) correlated linearly with absolute cerebral blood flow, consistent with high single-pass extraction of (11)C-dLop. AUC(10-30) correlated linearly with K(1).
conclusionP-gp function at the blood-brain barrier in humans can be quantified using PET and (11)C-dLop. A simple measure of brain uptake (AUC(10-30)) may be used as a surrogate of the fully quantified rate constant for brain entry (K(1)) and thereby avoid arterial sampling. However, to dissect the function of P-gp itself, both brain uptake and the influx rate constant must be corrected for radiotracer delivery (blood flow).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.