Abstract
The high-affinity phosphodiesterase-4 (PDE4) inhibitor R-rolipram and the less potent S-enantiomer, both labeled with 11C, were evaluated in vivo in rats. Regional brain uptake of R-[ 11C]rolipram was higher than R/S-[ 11C]rolipram, whereas S-[ 11C]rolipram retention subsided rapidly to levels below blood. Binding of R-[ 11C]rolipram was selective for PDE4 over PDE1, since treatment with PDE4 competitors Ro 20–1724, or R-, S- or R/S-rolipram, but not with the PDE1 inhibitor vinpocetine, significantly reduced radioactivity uptake to non-specific levels. R-Rolipram (ED 50 ≅ 0.04 mg/Kg) was approximately 13 fold more potent than S-rolipram at inhibiting R-[ 11C]rolipram binding in all brain regions. Nevertheless, S-[ 11C]rolipram appears to be unsuitable for measuring the non-specific binding of R-[ 11C]rolipram. Only unchanged R-[ 11C]rolipram was detected in rat brain homogenates. Additionally, the estimated absorbed radiation dose extrapolated to humans was low. These results support further investigation of R-[ 11C]rolipram in studying PDE4 in vivo by positron emission tomography imaging.
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