IMAGING

Nicolas TOURNIER

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Nicolas Tournier (PhD, PharmD) is hospital pharmacist and pharmacologist at the Centre Hospitalier Frédéric Joliot (CEA/SHFJ) in Orsay (France). He leads the Clinical Applications group of the IMIV research unit (Imagerie Moléculaire in Vivo - UMR 1023 Inserm/CEA/Université Paris Sud/Université Paris Saclay - ERL 9218 CNRS). The main aim of this group is to promote the clinical translation of original imaging probes and systems and develop their clinical applications. Their work builds upon the concept of pharmacological and pharmacokinetic imaging. They notably use radiolabeled analogues of drugs to study the impact of membrane transporters on tissue distribution and elimination, and estimate the corresponding risk of drug-drug interactions. To that end, the team benefits from a translational and multidisciplinary environment, making the best with recent developments in radiochemistry, medical physics, molecular imaging, nuclear medicine and pharmacokinetics.

Rifampicin inhibits glyburide uptake into hepatocytes

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Pharmaceuticals (Basel). 2022;15:587. Isotopic radiolabeling of the antiretroviral drug [18F]Dolutegravir for pharmacokinetic PET imaging. Tisseraud M, Goutal S, Bonasera T, Goislard M, Desjardins D, Le Grand R, Parry CM, Tournier N, Kuhnast B, Caillé F. PubMed

Pharmaceuticals (Basel). 2022;15:392. Pharmacokinetic imaging using 99mTc-Mebrofenin to untangle the pattern of hepatocyte transporter disruptions induced by endotoxemia in rats. Marie S, Hernández-Lozano I, Le Vée M, Breuil L, Saba W, Goislard M, Goutal S, Truillet C, Langer O, Fardel O, Tournier N. PubMed

J Cereb Blood Flow Metab. 2022;42:175-185. Comparative vulnerability of PET radioligands to partial inhibition of P-glycoprotein at the blood-brain barrier: A criterion of choice? Breuil L, Marie S, Goutal S, Auvity S, Truillet C, Saba W, Langer O, Caillé F, Tournier N. PubMed

Pharmaceutics. 2021;13:918. Imaging-based characterization of a Slco2b1(-/-) mouse model using [11C]Erlotinib and [99mTc]Mebrofenin as probe pubstrates. Marie S, Hernández-Lozano I, Breuil L, Truillet C, Hu S, Sparreboom A, Tournier N, Langer O. PubMed

J Nucl Med. 2021;62:1043-1047. Repurposing 99mTc-Mebrofenin as a Probe for Molecular Imaging of Hepatocyte Transporters. Marie S, Hernández-Lozano I, Langer O, Tournier N. PubMed

Pharm Res. 2021;38:127-140. Influence of Cation Transporters (OCTs and MATEs) on the renal and hepatobiliary disposition of [11C]Metoclopramide in mice. Hernández-Lozano I, Mairinger S, Sauberer M, Stanek J, Filip T, Wanek T, Ciarimboli G, Tournier N, Langer O. PubMed

Mol Imaging Biol. 2021;23:180-185. Human biodistribution and radiation dosimetry of the P-Glycoprotein radiotracer [11C]Metoclopramide. Bauer M, Barna S, Blaickner M, Prosenz K, Bamminger K, Pichler V, Tournier N, Hacker M, Zeitlinger M, Karanikas G, Langer O. PubMed

J Cereb Blood Flow Metab. 2020;In press. Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Tournier N, Goutal S, Mairinger S, Hernández-Lozano I, Filip T, Sauberer M, Caillé F, Breuil L, Stanek J, Freeman AF, Novarino G, Truillet C, Wanek T, Langer O. PubMed

Clin Pharmacol Ther. 2020;In press. Impaired clearance from the brain increases the brain exposure to metoclopramide in elderly subjects. Bauer M, Bamminger K, Pichler V, Weber M, Binder S, Maier-Salamon A, Tahir A, Jäger W, Haslacher H, Tournier N, Hacker M, Zeitlinger M, Langer O. PubMed

Nucl Med Biol. 2020;90-91:10-14. An original radio-biomimetic approach to synthesize radiometabolites for PET imaging. Auvity S, Breuil L, Goislard M, Bottlaender M, Kuhnast B, Tournier N, Caillé F. PubMed 

Pharmaceutics. 2020;12:486. Validation of pharmacological protocols for targeted inhibition of canalicular MRP2 activity in hepatocytes using [99mTc]mebrofenin imaging in rats. Marie S, Hernández-Lozano I, Breuil L, Saba W, Novell A, Gennisson JL, Langer O, Truillet C, Tournier N. PubMed

Nucl Med Biol. 2020;84-85:20-27. Automated two-step manufacturing of [11C]glyburide radiopharmaceutical for PET imaging in humans. Caillé F, Gervais P, Auvity S, Coulon C, Marie S, Tournier N, Kuhnast B. PubMed

J Nucl Med. 2020;61:1050-1057. Imaging P-glycoprotein induction at the Blood-Brain Barrier of a Beta-Amyloidosis mouse model with 11C-Metoclopramide PET. Zoufal V, Mairinger S, Brackhan M, Krohn M, Filip T, Sauberer M, Stanek J, Wanek T, Tournier N, Bauer M4, Pahnke J, Langer O. PubMed

Sci Rep. 2019;9:16310. Proof-of-Concept study of drug brain permeability between in vivo human brain and an in vitro iPSCs-Human Blood-Brain Barrier model. Roux GL, Jarray R, Guyot AC, Pavoni S, Costa N, Théodoro F, Nassor F, Pruvost A, Tournier N5, Kiyan Y, Langer O, Yates F, Deslys JP, Mabondzo A. PubMed

Neurology. 2019;92:813-814. 11C-glyburide PET imaging unveils the negligible brain penetration of glyburide in humans. Marie S, Comtat C, Caillé F, Becquemont L, Bottlaender M, Tournier N. PubMed

Clin Pharmacol Ther. 2019;105:1061-1064. Imaging P-Glycoprotein function at the Blood-Brain Barrier as a determinant of the variability in response to Central Nervous System drugs. Bauer M, Tournier N, Langer O. PubMed

Mol Pharm. 2019;16:1282-1293. Inhibition of ABCB1 and ABCG2 at the mouse Blood-Brain Barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Traxl A, Mairinger S, Filip T, Sauberer M, Stanek J, Poschner S, Jäger W, Zoufal V, Novarino G, Tournier N, Bauer M, Wanek T, Langer O. PubMed

J Nucl Med. 2019;60:985-991. Impact of P-glycoprotein function on the brain kinetics of the weak substrate 11C-Metoclopramide assessed with PET imaging in humans. Tournier N, Bauer M, Pichler V, Nics L, Klebermass EM, Bamminger K, Matzneller P, Weber M, Karch R, Caille F, Auvity S, Marie S, Jaeger W, Wadsak W, Hacker M, Zeitlinger M, Langer O. PubMed

Clin Pharmacol Ther. 2019;105:812-813. Impact of acute alcohol exposure on P-Glycoprotein function at the Blood-Brain Barrier assessed using 11 C-Metoclopramide PET imaging. Auvity S, Tournier N. PubMed

J Control Release. 2018;292:210-220. Physical blood-brain barrier disruption induced by focused ultrasound does not overcome the transporter-mediated efflux of erlotinib. Goutal S, Gerstenmayer M, Auvity S, Caillé F, Mériaux S, Buvat I, Larrat B, Tournier N. PubMed

J Nucl Med. 2019;60:486-491. A proof-of-concept study to inhibit ABCG2- and ABCB1-mediated efflux transport at the human blood-brain barrier. Bauer M, Karch R, Wulkersdorfer B, Philippe C, Nics L, Klebermass EM, Weber M, Poschner S, Haslacher H, Jäger W, Tournier N, Wadsak W, Hacker M, Zeitlinger M, Langer O. PubMed

Mol Pharm. 2018;15:4589-4598. Effect of rifampicin on the distribution of [11C]Erlotinib to the liver, a translational PET study in humans and in mice. Bauer M, Traxl A, Matsuda A, Karch R, Philippe C, Nics L, Klebermass EM, Wulkersdorfer B, Weber M, Poschner S, Tournier N, Jäger W, Wadsak W, Hacker M, Wanek T, Zeitlinger M, Langer O. PubMed

EJNMMI Res. 2018;8:81. Impact of rifampicin-inhibitable transport on the liver distribution and tissue kinetics of erlotinib assessed with PET imaging in rats. Amor D, Goutal S, Marie S, Caillé F, Bauer M, Langer O, Auvity S, Tournier N. PubMed

Contrast Media Mol Imaging. 2018;7310146. Positron Emission Tomography Imaging reveals an importance of saturable liver uptake transport for the pharmacokinetics of metoclopramide. Caillé F, Goutal S, Marie S, Auvity S, Cisternino S, Kuhnast B, Pottier G, Tournier N. PubMed

J Nucl Med. 2018; in press. P-glycoprotein (ABCB1) inhibits the influx and increases the efflux of 11C-metoclopramide across the blood-brain barrier: a PET study on non-human primates. Auvity S, Caillé F, Marie S, Wimberley C, Bauer M, Langer O, Buvat I, Goutal S, Tournier N. PubMed

Pharmacol Ther. 2018; in press. Imaging techniques to study drug transporter function in vivo. Tournier N, Stieger B, Langer O. PubMed

Drug Deliv Transl Res. 2018;8:536-542. Intravenous infusion for the controlled exposure to the dual ABCB1 and ABCG2 inhibitor elacridar in nonhuman primates. Goutal S, Langer O, Auvity S, Andrieux K, Coulon C, Caillé F, Gervais P, Cisternino S, Declèves X, Tournier N. PubMed

Pharm Sci. 2017;106:2335-2344. Imaging probes and modalities for the study of Solute Carrier O (SLCO)-transport function in vivo. Marie S, Cisternino S, Buvat I, Declèves X, Tournier N. PubMed

J Nucl Med. 2017;58:678-681. Assessment of P-Glycoprotein transport activity at the human blood-retina barrier with (R)-11C-Verapamil PET. Bauer M, Karch R, Tournier N, Cisternino S, Wadsak W, Hacker M, Marhofer P, Zeitlinger M, Langer O. PubMed

J Nucl Med. 2017;58:117-122. Strategies to inhibit ABCB1- and ABCG2-mediated efflux transport of erlotinib at the blood-brain barrier: a PET study in non-human primates. Tournier N, Goutal S, Auvity S, Traxl A, Mairinger S, Wanek T, Helal OB, Buvat I, Soussan M, Caillé F, Langer O. PubMed

J Cereb Blood Flow Metab. 2016; in press. Diphenhydramine as a selective probe to study H+-antiporter function at the blood-brain barrier: Application to [11C]diphenhydramine positron emission tomography imaging. Auvity S, Chapy H, Goutal S, Caillé F, Hosten B, Smirnova M, Declèves X, Tournier N, Cisternino S. PubMed

Eur J Pharm Sci. 2016;91:98-104. Imaging the impact of cyclosporin A and dipyridamole on P-glycoprotein (ABCB1) function at the blood-brain barrier: A [(11)C]-N-desmethyl-loperamide PET study in nonhuman primates. Damont A, Goutal S, Auvity S, Valette H, Kuhnast B, Saba W, Tournier N. PubMed

Antimicrob Agents Chemother. 2016;60:4734-42. Simultaneous Determination of Eight β-Lactam Antibiotics, Amoxicillin, Cefazolin, Cefepime, Cefotaxime, Ceftazidime, Cloxacillin, Oxacillin, and Piperacillin, in Human Plasma by Using Ultra-High-Performance Liquid Chromatography with Ultraviolet Detection. Legrand T, Vodovar D, Tournier N, Khoudour N, Hulin A. PubMed

J Pharm Biomed Anal. 2016;123:173-8. Validation of a simple HPLC-UV method for rifampicin determination in plasma: Application to the study of rifampicin arteriovenous concentration gradient. Goutal S, Auvity S, Legrand T, Hauquier F, Cisternino S, Chapy H, Saba W, Tournier N. PubMed

J Nucl Med. 2016;57:309-14. Imaging the impact of the P-Glycoprotein (ABCB1) function on the brain kinetics of metoclopramide. Pottier G, Marie S, Goutal S, Auvity S, Peyronneau MA, Stute S, Boisgard R, Dollé F, Buvat I, Caillé F, Tournier N. PubMed

Br J Pharmacol. 2016;173:497-510. Blood-brain and retinal barriers show dissimilar ABC transporter impacts and concealed effect of P-glycoprotein on a novel verapamil influx carrier. Chapy H, Saubaméa B, Tournier N, Bourasset F, Behar-Cohen F, Declèves X, Scherrmann JM, Cisternino S. PubMed

AAPS J. 2015;17:652-9. Influence of P-Glycoprotein inhibition or deficiency at the blood-brain barrier on (18)F-2-Fluoro-2-Deoxy-D-glucose ((18)F-FDG) brain kinetics. Tournier N, Saba W, Goutal S, Gervais P, Valette H, Scherrmann JM, Bottlaender M, Cisternino S. PubMed

Eur J Pharm Sci. 2013;50:520-5. [¹¹C]befloxatone brain kinetics is not influenced by Bcrp function at the blood-brain barrier: a PET study using Bcrp TGEM knockout rats. Hosten B, Boisgard R, Jacob A, Goutal S, Saubaméa B, Dollé F, Scherrmann JM, Cisternino S, Tournier N. PubMed

AAPS J. 2013;15:1082-90. Effects of selected OATP and/or ABC transporter inhibitors on the brain and whole-body distribution of glyburide. Tournier N, Saba W, Cisternino S, Peyronneau MA, Damont A, Goutal S, Dubois A, Dollé F, Scherrmann JM, Valette H, Kuhnast B, Bottlaender M. PubMed

Crit Care Med. 2012;40:3215-23. Respiratory toxicity of buprenorphine results from the blockage of P-glycoprotein-mediated efflux of norbuprenorphine at the blood-brain barrier in mice. Alhaddad H, Cisternino S, Declèves X, Tournier N, Schlatter J, Chiadmi F, Risède P, Smirnova M, Besengez C, Scherrmann JM, Baud FJ, Mégarbane B. PubMed

Pharm Res. 2012;29:2468-76. Discrepancies in the P-glycoprotein-mediated transport of (18)F-MPPF: a pharmacokinetic study in mice and non-human primates. Tournier N, Cisternino S, Peyronneau MA, Goutal S, Dolle F, Scherrmann JM, Bottlaender M, Saba W, Valette H. PubMed

Curr Pharm Des. 2011;17:2829-42. Opioid transport by ATP-binding cassette transporters at the blood-brain barrier: implications for neuropsychopharmacology. Tournier N, Declèves X, Saubaméa B, Scherrmann JM, Cisternino S. PubMed

J Nucl Med. 2011;52:415-23. Transport of selected PET radiotracers by human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2): an in vitro screening. Tournier N, Valette H, Peyronneau MA, Saba W, Goutal S, Kuhnast B, Dollé F, Scherrmann JM, Cisternino S, Bottlaender M. PubMed

Int J Neuropsychopharmacol. 2010;13:905-15. Interaction of drugs of abuse and maintenance treatments with human P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). Tournier N, Chevillard L, Megarbane B, Pirnay S, Scherrmann JM, Declèves X. PubMed

J Pharm Sci. 2009;98:4650-60. Ibogaine labeling with 99mTc-tricarbonyl: synthesis and transport at the mouse blood-brain barrier. Tournier N, André P, Blondeel S, Rizzo-Padoin N, du Moulinet d'Hardemarre A, Declèves X, Scherrmann JM, Cisternino S. PubMed

J Neurochem. 2009;108:767-75. Changes in dipole membrane potential at the mouse blood-brain barrier enhance the transport of 99mTechnetium Sestamibi more than inhibiting Abcb1, Abcc1, or Abcg2. Cattelotte J, Tournier N, Rizzo-Padoin N, Schinkel AH, Scherrmann JM, Cisternino S. PubMed