Title | ||
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Uptake and binding of the serotonin 5-HT1A antagonist [18F]-MPPF in brain of rats: Effects of the novel P-glycoprotein inhibitor tariquidar. |
Abstract | ||
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We used microPET to map the dose–response to the novel P-glycoprotein (P-gp) inhibitor tariquidar (TQD) of the initial influx of the P-gp substrate [18F]-MPPF in rat brain, and to test for effects of P-gp inhibition on the subsequent binding of [18F]-MPPF to serotonin 5-HT1A receptors. Summation maps of [18F]-MPPF uptake during the first 100 seconds after intravenous injection were calculated in groups of rats with vehicle (glucose 5%) pretreatment, or following pretreatment with TQD at doses of 5, 15, or 30 mg/kg. The early summation image (K1-weighted), were validated as a surrogate marker for the physiological blood–brain clearance (K1; ml g−1 min−1) by linear graphic analysis of the unidirectional blood–brain clearance relative to an image-based arterial input measured in the left ventricle of the heart. In the same animals, parametric maps of the [18F]-MPPF binding potential (BPND) were calculated from the entire 60-minute emission recordings using conventional reference tissue methods. All [18F]-MPPF recordings were followed by an [18F]-FDG emission recording, the summation of which was used for spatial normalization to a rat brain atlas. Test–retest variability of K1-weighted uptake and BPND was 25%. TQD treatment evoked a global dose-dependent increase in K1-weighted summation, which increased 2.5-fold with TQD (30 mg/kg), suggesting an IC50 of 5 mg/kg TQD. All TQD doses increased the apparent [18F]-MPPF BPND calculated by the Logan method by 30%–40%, a bias likely arising due to increased free [18F]-MPPF concentrations in brain. TQD (15 mg/kg) evoked a 45% global increase in [18F]-FDG uptake, suggesting perturbation of brain energy metabolism due to P-gp blockade. |
Year | DOI | Venue |
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2010 | 10.1016/j.neuroimage.2009.09.048 | NeuroImage |
Keywords | DocType | Volume |
P-glycoprotein,Tariquidar,[18F]-MPPF,[18F]-FDG,microPET | Journal | 49 |
Issue | ISSN | Citations |
2 | 1053-8119 | 0 |
PageRank | References | Authors |
0.34 | 6 | 16 |
Name | Order | Citations | PageRank |
---|---|---|---|
Christian la Fougère | 1 | 25 | 2.30 |
Guido Böning | 2 | 21 | 4.00 |
Hero Bartmann | 3 | 0 | 0.34 |
Björn Wängler | 4 | 0 | 0.34 |
Sebastian Nowak | 5 | 0 | 0.34 |
Theresa Just | 6 | 0 | 0.34 |
Erika Wagner | 7 | 0 | 0.34 |
Petra Winter | 8 | 0 | 0.34 |
Axel Rominger | 9 | 26 | 4.66 |
Stefan Förster | 10 | 30 | 6.99 |
Franz-Josef Gildehaus | 11 | 1 | 0.70 |
Pedro Rosa-Neto | 12 | 164 | 12.71 |
Luciano Minuzzi | 13 | 3 | 0.78 |
Peter Bartenstein | 14 | 47 | 8.83 |
Heidrun Potschka | 15 | 0 | 0.34 |
Paul Cumming | 16 | 50 | 10.13 |