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Functional Imaging of P-glycoprotein in the Blood–Brain Barrier with PET: State of the Art

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

The blood–brain barrier (BBB) is the main barrier between blood and brain. Its purpose is to maintain homeostasis in and protection of the central nervous system. Therefore, under normal physiological conditions, the BBB is impermeable for endotoxins, but also for exotoxins like drugs.

In the endothelial cells of the BBB, different active influx, but also active drug efflux transporters are presents. An example of drug efflux pumps is P‐glycoprotein (P‐gp) drug efflux pumps, which are encoded by MDR1 genes in humans.

A different P‐gp expression in the blood‐brain barrier can play a role in the aetiology of several brain disorders. For this reason, there is a need to develop an assay for the quantification P‐gp functionality in the BBB.

We discuss, the relationship of P‐gp and brain pathology and the involvement of age in loss of P‐gp function.

Furthermore, drugs treatment of brain diseases like Alzheimers's disease and Parkinson's disease are often not effective. Therefore, we discuss the relationship between P‐gp and drug availability.

In this chapter, an overview is given in the use of positron emission tomography as a tool for measuring P‐gp function in the area of neurology, neurophysiology and pharmacology.

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Abbreviations

Aβ:

beta‐amyloid

AD:

alzheimer's disease

ATP:

adenosine triphospate

BBB:

blood–brain barrier

CNS:

central nervous system

CsA:

cyclosporine A

4V:

fourth ventricle

LV:

lateral ventricle

MRI:

magnetic resonance image

MRP:

multidrug resistance-associated protein

NC:

nasal cavity

PET:

positron emission tomography

PD:

parkinson's disease

P‐gp:

P‐glycoprotein

PIT:

pituitary

SUV:

standard uptake value

V d :

volume of distribution

WT:

wild-type

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Authors
  1. N. H. Hendrikse
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  2. G. Luurtsema
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  3. B. N. M. van Berckel
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  4. E. J. F. Franssen
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  5. A. A. Lammertsma
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Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, New York, 10962, Orangeburg, USA

    Abel Lajtha

  2. Department of Psychiatry Millhauser Labs, Room MHL‐HN–604A, New York University School of Medicine, 550 First Avenue, N.Y. 10016, New York, USA

    Maarten E. A. Reith Ph.D.

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© 2007 Springer Science+Business Media, LLC.

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Hendrikse, N.H., Luurtsema, G., van Berckel, B.N.M., Franssen, E.J.F., Lammertsma, A.A. (2007). Functional Imaging of P-glycoprotein in the Blood–Brain Barrier with PET: State of the Art. In: Lajtha, A., Reith, M.E.A. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30380-2_5

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