11C-verapamil to assess P-gp function in human brain during aging, depression and neurodegenerative disease

Curr Top Med Chem. 2010;10(17):1775-84. doi: 10.2174/156802610792928059.

Abstract

P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a wide range of substrates from the brain. This is important for maintaining loco-regional homeostasis and for protecting the brain against blood-borne toxic substances. Altered P-gp function seems to be involved in the pathophysiology of neurodegenerative disease and various neurological and psychiatric disorders. Positron emission tomography (PET) with the radiotracer (11)C-verapamil (VPM-PET) is a validated technique allowing measurement of P-gp function at the human BBB. In this review, we highlight changes of P-gp function, as measured with VPM-PET, in aging and in the pathogenesis and progression of neurodegenerative disease, as well as their role in depressive disorders.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / chemistry
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Aging
  • Blood-Brain Barrier / diagnostic imaging*
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / physiopathology
  • Brain Diseases / diagnostic imaging*
  • Brain Diseases / metabolism
  • Brain Diseases / physiopathology
  • Carbon Radioisotopes
  • Depressive Disorder / diagnostic imaging*
  • Depressive Disorder / metabolism
  • Depressive Disorder / physiopathology
  • Humans
  • Neurodegenerative Diseases / diagnostic imaging*
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / physiopathology
  • Positron-Emission Tomography
  • Verapamil / chemistry
  • Verapamil / pharmacokinetics*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Carbon Radioisotopes
  • Verapamil