European Journal of Clinical Pharmacology

, Volume 65, Issue 9, pp 941–946 | Cite as

Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET

  • Martin Bauer
  • Rudolf Karch
  • Friederike Neumann
  • Aiman Abrahim
  • Claudia C. Wagner
  • Kurt Kletter
  • Markus Müller
  • Markus Zeitlinger
  • Oliver Langer
Short Communication

Abstract

Purpose

The aim of this study was to assess the influence of age on the functional activity of the multidrug efflux transporter P-glycoprotein (P-gp) at the human blood-brain barrier.

Methods

Seven young (mean age: 27 ± 4 years) and six elderly (mean age: 69 ± 9 years) healthy volunteers underwent dynamic (R)-[11C]verapamil (VPM) positron emission tomography (PET) scans and arterial blood sampling. Parametric distribution volume (DV) images were generated using Logan linearisation, and age groups were compared with statistical parametric mapping (SPM). Brain regions that SPM analysis had shown to be most affected by age were analysed by a region of interest (ROI)-based approach using a maximum probability brain atlas, before and after partial volume correction (PVC).

Results

SPM analysis revealed significant clusters of DV increases in cerebellum, temporal and frontal lobe of elderly compared to younger subjects. In the ROI-based analysis, elderly subjects showed significant DV increases in amygdala (+30%), insula (+26%) and cerebellum (+25%) before PVC, and in insula (+33%) after PVC.

Conclusions

Increased VPM DV values in the brains of elderly subjects suggest a decrease in cerebral P-gp function with increasing age.

Keywords

P-glycoprotein Blood-brain barrier Age (R)-[11C]verapamil Positron emission tomography 

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Martin Bauer
    • 1
  • Rudolf Karch
    • 2
  • Friederike Neumann
    • 2
  • Aiman Abrahim
    • 1
  • Claudia C. Wagner
    • 1
  • Kurt Kletter
    • 3
  • Markus Müller
    • 1
  • Markus Zeitlinger
    • 1
  • Oliver Langer
    • 1
    • 4
    • 5
  1. 1.Department of Clinical PharmacologyMedical University of ViennaViennaAustria
  2. 2.Department of Medical Computer SciencesMedical University of ViennaViennaAustria
  3. 3.Department of Nuclear MedicineMedical University of ViennaViennaAustria
  4. 4.Molecular MedicineAIT Austrian Institute of Technology GmbHSeibersdorfAustria
  5. 5.Department of Clinical Pharmacology, Division of Pharmacogenetics and ImagingMedical University of ViennaViennaAustria

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