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Imaging of P glycoprotein function in vivo with PET.

P glycoprotein (Pgp) is expressed on cell membranes of various organs in the body, such as the capillary endothelial cells of the brain. Furthermore, Pgp can also be expressed on the cell membrane of tumour cells. Because of Pgp-mediated efflux, tissue levels of several Pgp substrates are lower than in Pgp-negative tissues. Drug levels in Pgp-expressing organs may be increased by modulation of this Pgp-facilitated transport with several compounds, such as cyclosporin A. Up to now, the presence of drug efflux pumps in tissues could only be examined at the mRNA and protein level. However, this gives no insight into the important question of the functionality of these drug efflux pumps. Information about the transport function of Pgp and the effect of modulating this function may improve the therapeutic treatment of these patients. Positron emission tomography (PET) gives us a unique opportunity to study non-invasively (patho)physiological dynamic processes in vivo. We have therefore developed and validated a method for studying Pgp-mediated transport and its modulation in vivo with PET.