Translational pharmacokinetic imaging

In order to exert their pharmacological effects drugs have to reach the tissue targeted for treatment in which the drugs’ molecular targets are localized (e.g. receptor proteins, transporters, enzymes). In conventional pharmacokinetic studies drug concentrations are usually only measured in blood, which often does not allow to accurately predict a drug’s tissue concentration-time profile. Failure of a drug to reach its target tissue in sufficiently high concentrations is very often a reason for therapy failure. Positron emission tomography (PET) allows to measure the concentrations of drugs labeled with positron-emitting radionuclides (e.g. 11C, 18F) directly in tissue (e.g. brain, liver). The radioactive labelling of drug molecules and their preclinical evaluation is done in collaboration with the Radiochemistry and Biomarker Development and the Radiopharmacy and Experimental Nuclear Medicine Units. Next to clinical PET cameras, there is a dedicated small-animal PET system available at the Medical University of Vienna, which enables to assess the tissue distribution of drugs in a translational approach. Our projects span all the way from preclinical PET in healthy rodents and rodent disease models, over studies in healthy volunteers to studies in patients. Our projects are carried out in collaboration with the Department of Clinical Pharmacology at the Medical University of Vienna and the Austrian Institute of Technology.

Key publications (2005-2016)

• O Langer, R Karch, U Müller, G Dobrozemsky, A Abrahim, M Zeitlinger, E Lackner, C Joukhadar, R Dudczak, K Kletter, M Müller, M Brunner. Combined PET and microdialysis for in vivo assessment of intracellular drug pharmacokinetics in humans. J Nucl Med 46: 1835-1841 (2005)
  
  
• CC Wagner, M Bauer, R Karch, T Feurstein, S Kopp, P Chiba, K Kletter, W Löscher, M Müller, M Zeitlinger, O Langer. 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. J Nucl Med 50(12):1954-61 (2009)
  
  
• F Bauer, C Kuntner, JP Bankstahl, T Wanek, M Bankstahl, J Stanek, S  Mairinger, B Dörner, W Löscher, M Müller, T Erker, O Langer. Synthesis and in vivo evaluation of [¹¹C]tariquidar, a PET radiotracer based on a third-generation P-gp inhibitor. Bioorg Med Chem 18(15):5489-5497 (2010)
  
  
• CC Wagner, O Langer. Approaches using molecular imaging technology - use of PET in clinical microdose studies. Adv Drug Deliver Rev 63:539-546 (2011)
  
  
• M Bauer, M Zeitlinger, R Karch, P Matzneller, J Stanek, W Jäger, M Böhmdorfer, W Wadsak, M Mitterhauser, JP Bankstahl, W Löscher, M Koepp, C Kuntner, M Müller, O Langer. Pgp-mediated interaction between (R)-[¹¹C]verapamil and tariquidar at the human blood-brain barrier: a comparison with rat data. Clin Pharmacol Ther 91(2):227-233 (2012)
  
  
• T Wanek, C Kuntner, JP Bankstahl, S Mairinger, M Bankstahl, J Stanek, M Sauberer, T Filip, T Erker, M Müller, W Löscher, O Langer. A novel PET protocol for visualization of breast cancer resistance protein function at the blood-brain barrier. J Cereb Blood Flow Metab 32(11):2002-2011 (2012)
  
  
• M Bauer, R Karch, M Zeitlinger, J Stanek, C Philippe, W Wadsak, M Mitterhauser, W Jäger, H Haslacher, M Müller, O Langer. Interaction of 11C-tariquidar and 11C-elacridar with P-glycoprotein and breast cancer resistance protein at the human blood-brain barrier. J Nucl Med 54(8):1181-1187 (2013)
  
  
• M Bauer, R Karch, M Zeitlinger, J Liu, MJ Koepp, M-C Asselin, SM Sisodiya, JA Hainfellner, W Wadsak, M Mitterhauser, M Müller, E Pataraia, O Langer. In vivo P-glycoprotein function before and after epilepsy surgery. Neurology 83:1326-31 (2014)
  
  
• M Bauer, R Karch, M Zeitlinger, C Philippe, K Römermann, J Stanek, A Maier-Salamon, W Wadsak, W Jäger, M Hacker, M Müller, O Langer. Approaching complete inhibition of P-glycoprotein at the human blood-brain barrier: an (R)-[¹¹C]verapamil PET study. J Cereb Blood Flow Metab 35:743-746 (2015)
  
  
• A Traxl, T Wanek, S Mairinger, J Stanek, T Filip, M Sauberer, M Müller, C Kuntner, O Langer. Breast cancer resistance protein and p-glycoprotein influence in vivo disposition of 11C-erlotinib. J Nucl Med 56(12):1930-1936 (2015)
  
  
• M Bauer, K Römermann, R Karch, B Wulkersdorfer, J Stanek, C Philippe, A Maier-Salamon, H Haslacher, C Jungbauer, W Wadsak, W Jäger, W Löscher, M Hacker, M Zeitlinger, O Langer. Pilot PET study to assess the functional interplay between ABCB1 and ABCG2 at the human blood-brain barrier. Clin Pharmacol Ther 100:131-141 (2016)