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...
| Publicado en: | Molecular Imaging & Biology Vol. 14; no. 2; pp. 225 - 237 |
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| Autores principales: | , , , , , , , , , , , , , , , |
| Formato: | research Journal Article |
| Publicado: |
Springer Nature
Apr2012
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| Acceso en línea: | Ver este registro en EBSCOhost |
| Sumario: | 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. |
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