Abstract
1193
Objectives The efflux transporter P-glycoprotein (P-gp) is expressed in the blood-brain barrier (BBB) and protects the brain from xenobiotics. Animal data suggest regional differences in cerebral P-gp activity. (R)-[11C]verapamil (VPM) PET can be used to measure P-gp-mediated transport at the BBB, but low brain uptake of VPM hampers the mapping of regional P-gp function. This limitation can be overcome by P-gp modulation with moderate doses of P-gp inhibitors. We assessed regional P-gp function in humans before and after P-gp modulation with tariquidar (TQD).
Methods 5 healthy volunteers underwent a VPM PET baseline scan and a second scan at 3h after TQD administration (2 mg/kg). Parametric images depicting distribution volume (DV) differences between the 2 scans were generated using the pixel-wise Logan plot and analyzed by statistical parametric mapping (SPM5).
Results Significantly smaller DV increases were observed in cerebellum, hippocampus, parahippocampus, enthorinal cortex, inferior temporal lobe, and brain stem as compared to other brain regions, which points to increased P-gp expression and function in these regions. In choroid plexus the smallest DV increases were found in response to TQD.
Conclusions Regional differences in VPM DV changes in response to TQD treatment suggest regional variability of cerebral P-gp function, which might make some brain areas more resistant and others more vulnerable to the accumulation of P-gp substrates. Minor DV changes in choroid plexus, where P-gp transport is supposed to occur in opposite direction, questions significant P-gp mediated transport of VPM at the blood-CSF barrier.
Research Support The research leading to these results has received funding from the European Community´s Seventh Framework Programme under grant agreement no. 201380 (EURIPIDES).
- © 2009 by Society of Nuclear Medicine