Characterization of r-[11C]rolipram for PET imaging of phosphodieterase-4: in vivo binding, metabolism, and dosimetry studies in rats

Nucl Med Biol. 2001 May;28(4):347-58. doi: 10.1016/s0969-8051(01)00206-2.


The high-affinity phosphodiesterase-4 (PDE4) inhibitor R-rolipram and the less potent S-enantiomer, both labeled with (11)C, were evaluated in vivo in rats. Regional brain uptake of R-[(11)C]rolipram was higher than R/S-[(11)C]rolipram, whereas S-[(11)C]rolipram retention subsided rapidly to levels below blood. Binding of R-[(11)C]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) congruent with 0.04 mg/Kg) was approximately 13 fold more potent than S-rolipram at inhibiting R-[(11)C]rolipram binding in all brain regions. Nevertheless, S-[(11)C]rolipram appears to be unsuitable for measuring the non-specific binding of R-[(11)C]rolipram. Only unchanged R-[(11)C]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-[(11)C]rolipram in studying PDE4 in vivo by positron emission tomography imaging.

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism*
  • Animals
  • Binding, Competitive / drug effects
  • Carbon Radioisotopes
  • Cyclic Nucleotide Phosphodiesterases, Type 1
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Half-Life
  • Isotope Labeling
  • Male
  • Phosphodiesterase Inhibitors* / pharmacokinetics
  • Radiometry
  • Radiopharmaceuticals* / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Rolipram* / pharmacokinetics
  • Stereoisomerism
  • Tissue Distribution
  • Tomography, Emission-Computed


  • Carbon Radioisotopes
  • Phosphodiesterase Inhibitors
  • Radiopharmaceuticals
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 1
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Rolipram