In the past, great achievements in the understanding of compound distribution have been made by measuring plasma concentrations. Organ concentrations were not available. With the emerging knowledge of hepatocyte membrane transporters, it is clear that, depending on the relative hepatocyte influx and efflux clearances of compounds, unbound hepatocyte concentrations can exceed, equal, or be lower than unbound plasma concentrations. Disconnection between hepatocyte and plasma concentrations of various endogenous or exogenous compounds becomes even more unpredictable when the expression and functions of membrane transporters are altered during liver diseases.

The topic focuses on transporter imaging. All imaging modalities are used to study the function of hepatocyte membrane transporters. However, nuclear imaging is the primary modality in clinical studies, with 24 clinical trials currently listed in the United States and in Europe PubMed. All articles published in 2016 are highlighted. Reviews published between 2013 and 2015 summarise the importance of the subject.


  • Bioorg Med Chem. 2016; in press. Design, synthesis, in vitro characterization and preliminary imaging studies on fluorinated bile acid derivatives as PET tracers to study hepatic transporters. Testa A, Dall'Angelo S, Mingarelli M, Augello A, Schweiger L, Welch A, Elmore CS, Sharma P, Zanda M. PubMed
  • Nucl Med Biol. 2016;43:642-9. Synthesis, in vitro and in vivo small-animal SPECT evaluation of novel technetium labeled bile acid analogues to study (altered) hepatic transporter function. Neyt S, Vliegen M, Verreet B, De Lombaerde S, Braeckman K, Vanhove C, Huisman MT, Dumolyn C, Kersemans K, Hulpia F, Van Calenbergh S, Mannens G, De Vos F. PubMedJ Pharm Sci. 2016;105:106-12. Influence of 24-nor-ursodeoxycholic acid on hepatic disposition of [(18)F]ciprofloxacin, a Positron Emission Tomography study in mice. Wanek T, Halilbasic E, Visentin M, Mairinger S, Römermann K, Stieger B, Kuntner C, Müller M, Langer O, Trauner M. PubMed
  • Curr Pharm Des. 2016; in press. PET tracers for imaging of ABC transporters at the blood-brain barrier: principles and strategies. Luurtsema G, Elsinga P, Dierckx R, Boellaard R, van Waarde A. PubMed
  • PLoS One. 2016;11:e0161427. Identification of ABC transporter interaction of a novel cyanoquinoline radiotracer and implications for tumour imaging by Positron Emission Tomography. Slade RL, Pisaneschi F, Nguyen QD, Smith G, Carroll L, Beckley A, Kaliszczak MA, Aboagye EO. PubMed
  • J Clin Pharmacol. 2016;56:S143-56. Use of PET imaging to evaluate transporter-mediated drug-drug Interactions. Langer O. PubMed
  • Clin Pharmacol Ther. 2016;100:479-488.  Imaging transporters: transforming diagnostic and therapeutic development. Mann A, Han H, Eyal S. PubMed
  • J Nucl Med. 2016;57:615-21. A PET tracer for renal Organic Cation Transporters, ¹¹C-Metformin: radiosynthesis and preclinical proof-of-concept studies. Jakobsen S, Busk M, Jensen JB, Munk OL, Zois NE, Alstrup AK, Jessen N, Frøkiær J. PubMed
  • J Nucl Med. 2016;57:309-14. Imaging the mpact 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
  • EJNMMI Res. 2016;6:54. Renal PET-imaging with (11)C-metformin in a transgenic mouse model for chronic kidney disease. Pedersen L, Jensen JB, Wogensen L, Munk OL, Jessen N, Frøkiær J, Jakobsen S. PubMed


  • Eur J Drug Metab Pharmacokinet. 2016; in press. Liver perfusion modifies Gd-DTPA and Gd-BOPTA hepatocyte concentrations through transfer clearances across sinusoidal membranes. Daire JL, Leporq B, Vilgrain V, Van Beers BE, Schmidt S, Pastor CM. PubMed
  • J Hepatol. 2016;64:708-16. Insights into the diagnosis of hepatocellular carcinomas with hepatobiliary MRI. Vilgrain V, Van Beers BE, Pastor CM. PubMed

2013-2015 REVIEWS

  • AAPS J. 2015;17:788-801. Molecular imaging of membrane transporters' activity in cancer: a picture is worth a thousand tubes. Mann A, Semenenko I, Meir M, Eyal S. PubMed
  • Expert Opin Drug Metab Toxicol. 2015;11:1233-51. Nature and uses of fluorescent dyes for drug transporter studies. Fardel O, Le Vee M, Jouan E, Denizot C, Parmentier Y. PubMed
  • Mol Pharm. 2015;12:2203-16. PET tracers to study clinically relevant hepatic transporters.Testa A, Zanda M, Elmore CS, Sharma P. PubMed
  • Clin Pharmacol Ther. 2015;97:362-71. Radiopharmaceuticals for assessing ABC transporters at the blood-brain barrier. Raaphorst RM, Windhorst AD, Elsinga PH, Colabufo NA, Lammertsma AA, Luurtsema G. PubMed
  • Clin Pharmacokinet. 2015;54:225-42. Drug transporters in the central nervous system. Stieger B, Gao B. PubMed
  • Drug Metab Dispos. 2014;42:2007-15. Role of (drug) transporters in imaging in health and disease. Stieger B, Unadkat JD, Prasad B, Langer O, Gali H. PubMed
  • Clin Pharmacol Ther. 2014;96:206-13. Using Positron Emission Tomography to study transporter-mediated drug-drug interactions in tissues. Wulkersdorfer B, Wanek T, Bauer M, Zeitlinger M, Müller M, Langer O. PubMed
  • Drug Metab Dispos. 2014;42:675-84. The role of organic anion transporters in diagnosing liver diseases by Magnetic Resonance Imaging. Pastor CM, Müllhaupt B, Stieger B. PubMed
  • ChemMedChem. 2014;9:38-42. PET radiotracers for imaging P-glycoprotein: the challenge for early diagnosis in AD.Leopoldo M, Contino M, Berardi F, Perrone R, Colabufo NA. PubMed
  • Clin Pharmacol Ther. 2013;94:80-94. Why clinical modulation of efflux transport at the human blood-brain barrier is unlikely: the ITC evidence-based position. Kalvass JC, Polli JW, Bourdet DL, Feng B, Huang SM, Liu X, Smith QR, Zhang LK, Zamek-Gliszczynski MJ; International Transporter Consortium. PubMed
  • ACS Chem Neurosci. 2013;4:225-37. Advances in PET imaging of P-glycoprotein function at the blood-brain barrier. Syvänen S, Eriksson J. PubMed
  • Clin Pharmacol Ther. 2013;93:263-6. Intracellular drug concentrations. Dollery CT. PubMed