Detail

Keywords

ATP-Binding Cassette Transporters; Blood-Brain Barrier; Central Nervous System; Drug Carriers; Drug Development; Drug Interactions; Kidney; Liver; Lung; Membrane Transport Proteins; Nuclear Medicine; Pharmacokinetics; Pharmacology, Clinical; Positron-Emission Tomography; Radionuclide Imaging; Tissue Distribution

Research group(s)

• Section of Clinical Pharmacokinetics / Pharmacogenetics and Imaging
  Head: Markus Zeitlinger
  Research Area: Our main focus is the study of the drug distribution process by employing techniques to measure target site distribution directly, i.e. PET or microdialysis.
  Members:
  Oliver Langer
  Valentin al Jalali
  Severin Mairinger
  Alina Nussbaumer-Pröll
• Translational Pharmacokinetic Imaging
  Head: Oliver Langer
  Members:
  Oliver Langer
  Severin Mairinger

Research interests

In my research I use positron emission tomography (PET) imaging with radiolabeled drug molecules to assess factors governing the tissue distribution and excretion of drugs in health and disease with a special emphasis on the action of membrane transporters belonging to the ATP-binding cassette (ABC) and solute carrier (SLC) families. My research covers preclinical and clinical PET studies in healthy rodents, rodent disease models (Alzheimer's disease, epilepsy), healthy human volunteers and patients. I am also interested in the development of new PET imaging protocols to measure the activity of ABC and SLC transporters in different organs (brain, eye, liver, kidneys, lungs) and in the development of strategies to enhance the brain distribution of moleculary targeted anticancer drugs.

Techniques, methods & infrastructure

Preclinical and clinical positron emission tomography (PET); radiotracer development; radiochemistry; carbon-11 and fluorine-18 labelling; pharmacokinetic modeling; quantitative image analysis; in vitro transport experiments; autoradiography; metabolite analysis

Grants

• Effect of OCT/Ns on pulmonary disposition of inhaled drugs (2023)
  Source of Funding: FWF (Austrian Science Fund), Stand-alone project
  Principal Investigator
• Effect of OCT/Ns on pulmonary disposition of inhaled drugs (2023)
  Source of Funding: FWF (Austrian Science Fund), stand-alone project - P 36738-B
  Principal Investigator
• PETABC (2020)
  Source of Funding: FFG (Austrian Research Promotion Agency), JPND transnational call: “Novel imaging and brain stimulation methods and technologies related to Neurodegenerative Diseases (JPND2020) - JPND2020-568-081
  Principal Investigator
• Use of PET to study the effect of antihypertensive drugs on lung-specific expression of ACE2, the cellular entry point of SARS-CoV-2 (2020)
  Source of Funding: FWF (Austrian Science Fund), Stand-alone project (Urgent Funding SARS-CoV-2) - P 33921
  Principal Investigator
• A pilot study to assess the impact of ABCB1 on the neuropharmacokinetics of the weak ABCB1 substrate [11C]metoclopramide (2018)
  Source of Funding: FWF (Austrian Science Fund), KLIF - KLI 694-B30
  Principal Investigator
• PET imaging to assess the role of membrane transporters in pulmonary disposition of inhaled drugs (2018)
  Source of Funding: NÖ Forschungs- und Bildungsges.m.b.H. (NFB), Life Sciences
  Principal Investigator
• Improving brain distribution of drugs targeted to the brain (2016)
  Source of Funding: NÖ Forschungs- und Bildungsges.m.b.H. (NFB), Life Sciences
  Principal Investigator
• Influence of ABCG2 SNP on brain distribution of ABCG2 substrates (2015)
  Source of Funding: FWF (Austrian Science Fund), KLIF - KLI 480-B30
  Principal Investigator
• PET imaging to assess BBB function in Alzheimer’s disease (2014)
  Source of Funding: FWF (Austrian Science Fund), DACH project - I 1609-B24
  Principal Investigator
• Species differences in Pgp function at the BBB (2012)
  Source of Funding: FWF (Austrian Science Fund), stand-alone project - P24894-B24
  Principal Investigator
• Euripides (2008)
  Source of Funding: EU, FP7 collaborative project - grant agreement nr. 201380
  Principal Investigator

Selected publications

1. Bauer, M. et al., 2020. Impaired Clearance From the Brain Increases the Brain Exposure to Metoclopramide in Elderly Subjects. Clinical Pharmacology & Therapeutics. Available at: http://dx.doi.org/10.1002/cpt.2052.
2. Mairinger, S. et al., 2020. Assessing the Activity of Multidrug Resistance–Associated Protein 1 at the Lung Epithelial Barrier. Journal of Nuclear Medicine, 61(11), pp.1650–1657. Available at: http://dx.doi.org/10.2967/jnumed.120.244038.
3. Zoufal, V. et al., 2019. Imaging P-Glycoprotein Induction at the Blood–Brain Barrier of a β-Amyloidosis Mouse Model with 11C-Metoclopramide PET. Journal of Nuclear Medicine, 61(7), pp.1050–1057. Available at: http://dx.doi.org/10.2967/jnumed.119.237198.
4. Bauer, M. et al., 2017. Influence of OATPs on Hepatic Disposition of Erlotinib Measured With Positron Emission Tomography. Clinical Pharmacology & Therapeutics, 104(1), pp.139–147. Available at: http://dx.doi.org/10.1002/cpt.888.
5. Hernández-Lozano, I. et al. (2022) ‘PET imaging to assess the impact of P-glycoprotein on pulmonary drug delivery in rats’, Journal of Controlled Release, 342, pp. 44–52. Available at: http://dx.doi.org/10.1016/j.jconrel.2021.12.031.