Analysis of (R)- and (S)-[(11)C]rolipram kinetics in canine myocardium for the evaluation of phosphodiesterase-4 with PET.

Purpose: (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.Procedures: Seven dogs underwent (R)-[(11)C]rolipram...

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Publicado en:Molecular Imaging & Biology Vol. 14; no. 2; pp. 225 - 237
Autores principales: Lortie M, DaSilva JN, Kenk M, Thorn S, Davis D, Birnie D, Beanlands RS, deKemp RA, Lortie, Mireille, DaSilva, Jean N, Kenk, Miran, Thorn, Stephanie, Davis, Darryl, Birnie, David, Beanlands, Rob S B, deKemp, Robert A
Formato: research Journal Article
Publicado: Springer Nature Apr2012
Acceso en línea:Ver este registro en EBSCOhost
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      jtl: Molecular Imaging & Biology
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      dt: Apr2012
      vid: 14
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s11307-011-0482-6
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        atl: Analysis of (R)- and (S)-[(11)C]rolipram kinetics in canine myocardium for the evaluation of phosphodiesterase-4 with PET.
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        au:
          Lortie M
          DaSilva JN
          Kenk M
          Thorn S
          Davis D
          Birnie D
          Beanlands RS
          deKemp RA
          Lortie, Mireille
          DaSilva, Jean N
          Kenk, Miran
          Thorn, Stephanie
          Davis, Darryl
          Birnie, David
          Beanlands, Rob S B
          deKemp, Robert A
        affil: Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada, K1Y 4W7
      sug:
        subj:
          Esterases Metabolism
          Heterocyclic Compounds
          Heterocyclic Compounds Pharmacokinetics
          Myocardium
          Tomography, Emission-Computed Methods
          Animal Studies
          Chemistry
          Dogs
          Heterocyclic Compounds Blood
          Models, Biological
          Radioisotopes Diagnostic Use
          Time Factors
      ab: Purpose: (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.Procedures: 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%).Conclusion: 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.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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