Analysis of (R)- and (S)-[11C]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]roli...

Full description

Saved in:
Bibliographic Details
Published in:Molecular imaging and biology 2012-04, Vol.14 (2), p.225-236
Main Authors: Lortie, Mireille, DaSilva, Jean N., Kenk, Miran, Thorn, Stephanie, Davis, Darryl, Birnie, David, Beanlands, Rob S. B., deKemp, Robert A.
Format: Article
Language:English
Subjects:
Animals
Carbon Radioisotopes
Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism
Data processing
Dogs
Enantiomers
Imaging
Kinetics
Medicine
Medicine & Public Health
Metabolites
Models, Biological
Myocardium
Myocardium - enzymology
Positron-Emission Tomography - methods
Radiology
Research Article
Rolipram - blood
Rolipram - chemistry
Rolipram - pharmacokinetics
Stereoisomerism
Time Factors
Tracers
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1536-1632
1860-2002
DOI:10.1007/s11307-011-0482-6