ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2009
Imaging of cyclosporine inhibition of P-glycoprotein activity using 11C-verapamil in the brain: studies of healthy humans.
Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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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
69 citing papers in PubMed, 128 citations in OpenAlex.
- P-Glycoprotein and Breast Cancer Resistance Protein Transporter Inhibition by Cyclosporine and Quinidine on the Pharmacokinetics of Oral Rimegepant in Healthy Subjects.Clinical pharmacology in drug development · 2022Trial
- Positron Emission Tomography Imaging of [Clinical pharmacology and therapeutics · 2019Trial
- Impact of P-Glycoprotein Function on the Brain Kinetics of the Weak SubstrateJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019Trial
- 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
- P-glycoprotein function at the blood-brain barrier: effects of age and gender.Molecular imaging and biology · 2012Trial
- A pilot study to assess the efficacy of tariquidar to inhibit P-glycoprotein at the human blood-brain barrier with (R)-11C-verapamil and PET.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2009Trial
- AAngewandte Chemie (International ed. in English) · 2026Article
- A dual-pronged host-directed therapeutic targeting cyclophilin A and pathogenic interferon response abrogates virus-triggered pregnancy pathologies.Nature communications · 2026Article
- Effective Brain Targeting Using the Self-Emulsifying Drug Delivery Systems.AAPS PharmSciTech · 2026Review
- Measurement of cyclosporin induced changes in P-glycoprotein function at the human blood-brain barrier using [European journal of nuclear medicine and molecular imaging · 2025Article
- Designing a Small Molecule for PET Radiotracing: [Molecules (Basel, Switzerland) · 2025Review
- Nose-to-Brain (N2B) Delivery: An Alternative Route for the Delivery of Biologics in the Management and Treatment of Central Nervous System Disorders.Pharmaceutics · 2023Review
- Cardiac PET Imaging of ATP Binding Cassette (ABC) Transporters: Opportunities and Challenges.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Parametric Imaging of P-Glycoprotein Function at the Blood-Brain Barrier Using kMolecular imaging and biology · 2023Article
- Synergistic Inhibitory Effect of Quercetin and Cyanidin-3O-Sophoroside on ABCB1.International journal of molecular sciences · 2023Article
- Intravenous and oral whole body ketone dosimetry, biodistribution, metabolite correction and kinetics studied by (R)-[1-EJNMMI radiopharmacy and chemistry · 2023Article
- PET AIF estimation when available ROI data is impacted by dispersive and/or background effects.Physics in medicine and biology · 2023Article
- Patient-Adaptive Population-Based Modeling of Arterial Input Functions.IEEE transactions on medical imaging · 2023Article
- Transport Mechanisms at the Blood-Brain Barrier and in Cellular Compartments of the Neurovascular Unit: Focus on CNS Delivery of Small Molecule Drugs.Pharmaceutics · 2022Review
- 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
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledThe multiple-drug resistance (MDR) transporter P-glycoprotein (P-gp) is highly expressed at the human blood-brain barrier (BBB). P-gp actively effluxes a wide variety of drugs from the central nervous system, including anticancer drugs. We have previously demonstrated P-gp activity at the human BBB using PET of (11)C-verapamil distribution into the brain in the absence and presence of the P-gp inhibitor cyclosporine-A (CsA). Here we extend the initial noncompartmental analysis of these data and apply compartmental modeling to these human verapamil imaging studies.
methodsHealthy volunteers were injected with (15)O-water to assess blood flow, followed by (11)C-verapamil to assess BBB P-gp activity. Arterial blood samples and PET images were obtained at frequent intervals for 5 and 45 min, respectively, after injection. After a 60-min infusion of CsA (intravenously, 2.5 mg/kg/h) to inhibit P-gp, a second set of water and verapamil PET studies was conducted, followed by (11)C-CO imaging to measure regional blood volume. Blood flow was estimated using dynamic (15)O-water data and a flow-dispersion model. Dynamic (11)C-verapamil data were assessed by a 2-tissue-compartment (2C) model of delivery and retention and a 1-tissue-compartment model using the first 10 min of data (1C(10)).
resultsThe 2C model was able to fit the full dataset both before and during P-pg inhibition. CsA modulation of P-gp increased blood-brain transfer (K(1)) of verapamil into the brain by 73% (range, 30%-118%; n = 12). This increase was significantly greater than changes in blood flow (13%; range, 12%-49%; n = 12, P < 0.001). Estimates of K(1) from the 1C(10) model correlated to estimates from the 2C model (r = 0.99, n = 12), indicating that a short study could effectively estimate P-gp activity.
conclusion(11)C-verapamil and compartmental analysis can estimate P-gp activity at the BBB by imaging before and during P-gp inhibition by CsA, indicated by a change in verapamil transport (K(1)). Inhibition of P-gp unmasks verapamil trapping in brain tissue that requires a 2C model for long imaging times; however, transport can be effectively measured using a short scan time with a 1C(10) model, avoiding complications with labeled metabolites and tracer retention.
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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.