title: Analysis of (R)- and (S)-[(11)C]rolipram kinetics in canine myocardium for the evaluation of phosphodiesterase-4 with PET.
abstract: OBJECTIVE
  (R)-[(11)C]rolipram and (S)-[(11)C]rolipram have been proposed to investigate phosphodiesterase-4 and, indirectly, cAMP-mediated signaling with PET. This study assessed binding of these tracers to phosphodiesterase-4 in canine myocardium.
  
  
  METHODS
  Seven dogs underwent (R)-[(11)C]rolipram and (S)-[(11)C]rolipram dynamic PET imaging at baseline and with co-injection of saturating doses of (R)-rolipram. Dual-input compartment models were applied to estimate the volumes of distribution (V(T)).
  
  
  RESULTS
  The model comprising one compartment for unmetabolized tracer and one compartment for labeled metabolites provided excellent fits to data acquired with (S)-[(11)C]rolipram at baseline and with both enantiomers during co-injection scans. Use of two compartments for unmetabolized (R)-[(11)C]rolipram at baseline was warranted according to Akaike and Schwarz criteria. V(T) estimates obtained with these models were robust (CV ≤ 8.2%) and reproducible (CV ≤ 15%).
  
  
  CONCLUSIONS
  An important fraction (~65%) of the V (T) of (R)-[(11)C]rolipram at baseline reflects specific binding. Thus, the latter may be a useful index of phosphodiesterase-4 levels in canine myocardium.
authors.affiliation: Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada, K1Y 4W7. mlortie@ottawaheart.ca
authors.forename: Mireille
authors.initials: M
authors.lastname: Lortie
authors.forename: Jean N
authors.initials: JN
authors.lastname: DaSilva
authors.forename: Miran
authors.initials: M
authors.lastname: Kenk
authors.forename: Stephanie
authors.initials: S
authors.lastname: Thorn
authors.forename: Darryl
authors.initials: D
authors.lastname: Davis
authors.forename: David
authors.initials: D
authors.lastname: Birnie
authors.forename: Rob S B
authors.initials: RS
authors.lastname: Beanlands
authors.forename: Robert A
authors.initials: RA
authors.lastname: deKemp
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D004285:Dogs; D008954:Models, Biological; D009206:Myocardium / Q000201:enzymology*; D049268:Positron-Emission Tomography / Q000379:methods*; D020889:Rolipram / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D002250:Carbon Radioisotopes; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram