Analysis of ( R )- and ( S )-[ 11 C]rolipram Kinetics in Canine Myocardium for the Evaluation of Phosphodiesterase-4 with PET

Author： Lortie Mireille

Publisher： Springer Publishing Company

ISSN： 1536-1632

Source： Molecular Imaging and Biology, Vol.14, Iss.2, 2012-04, pp. : 225-236

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Abstract

(R)-[¹¹C]rolipram and (S)-[¹¹C]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.Seven dogs underwent (R)-[¹¹C]rolipram and (S)-[¹¹C]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).The model comprising one compartment for unmetabolized tracer and one compartment for labeled metabolites provided excellent fits to data acquired with (S)-[¹¹C]rolipram at baseline and with both enantiomers during co-injection scans. Use of two compartments for unmetabolized (R)-[¹¹C]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%).An important fraction (~65%) of the V _T of (R)-[¹¹C]rolipram at baseline reflects specific binding. Thus, the latter may be a useful index of phosphodiesterase-4 levels in canine myocardium.