Imaging the function of P-glycoprotein with radiotracers: pharmacokinetics and in vivo applications

Clin Pharmacol Ther. 2009 Oct;86(4):368-77. doi: 10.1038/clpt.2009.138. Epub 2009 Jul 22.


P-glycoprotein (P-gp), an efflux transporter, controls the pharmacokinetics of various compounds under physiological conditions. P-gp-mediated drug efflux has been suggested as playing a role in various disorders, including multidrug-resistant cancer and medication-refractory epilepsy. However, P-gp inhibition has had, to date, little or no clinically significant effect in multidrug-resistant cancer. To enhance our understanding of its in vivo function under pathophysiological conditions, substrates of P-gp have been radiolabeled and imaged using single-photon emission computed tomography (SPECT) and positron emission tomography (PET). To accurately quantify P-gp function, a radiolabeled P-gp substrate should be selective for P-gp, produce a large signal after P-gp blockade, and generate few radiometabolites that enter the target tissue. Furthermore, quantification of P-gp function via imaging requires pharmacological inhibition of P-gp, which requires knowledge of P-gp density at the target site. By meeting these criteria, imaging can elucidate the function of P-gp in various disorders and improve the efficacy of treatments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Biological Transport / physiology
  • Blood-Brain Barrier / metabolism
  • Drug Resistance, Multiple
  • Epilepsy / drug therapy
  • Epilepsy / metabolism
  • Humans
  • Models, Biological
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism
  • Pharmacokinetics
  • Positron-Emission Tomography
  • Radiopharmaceuticals* / pharmacokinetics
  • Tomography, Emission-Computed, Single-Photon


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Radiopharmaceuticals