Abstract
1198
Objectives To establish a microPET assay for the uptake and binding of the 5-HT1A antagonist [18F]-MPPF in rat brain, and determine the dose-response of this uptake to the novel P-glycoprotein (P-gp) inhibitor tariquidar (TQD). Parametric-mapping was used to calculate the initial [18F]-MPPF influx and the specific binding (BPND) in rats.
Methods K1-weighted maps were calculated from the initial (2 min) [18F]-MPPF-uptake after tracer-injection, and BPND was calculated from the entire 60 minute emission recordings using Logan’s graphical analysis as well as SRTM. [18F]-MPPF recordings were followed by a [18F]-FDG-recording, the summation of which was used for normalization to a rat brain-atlas. Test-retest-stability of K1-weighted uptake and BPND, and effects of vehicle-injection or TQD (15 mg/kg, i.v.) were assessed in one group (N=6), in four scanning sessions. Similar examination of TQD-effects (5 and 30 mg/kg) were made in another group (N=6).
Results Test-retest-variability of K1-weighted-uptake and BPND were 25%. TQD-medication evoked a dose-dependent increase in K1-weighted-uptake, suggesting an IC50 close to 5 mg/kg, and an increase by 250% of initial uptake at the highest administered TQD-dose. All TQD-doses increased the apparent BPND in hippocampus by 30–40%. In addition, the intermediate TQD-dose (15 mg/kg) increased the [18F]-FDG uptake by 45%.
Conclusions Dose-dependent modulation of P-gp activity by TQD can be measured noninvasesively in rat brain by [18F]-MPPF and microPET. K1-weighted-uptake was affected significantly by TQD-premedication.
- © 2009 by Society of Nuclear Medicine