Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9197891 | NeuroImage | 2005 | 10 Pages |
Abstract
Objective: Phosphodiesterase 4 (PDE4) catabolizes the second messenger 3â², 5â²-cyclic adenosine monophosphate and may play a critical role in brain diseases. Our aim was to quantify PDE4 in rats with positron emission tomography (PET). Methods: High (n = 6) and low specific activity (SA) (n = 2) higher affinity ((R)-[11C]rolipram) and high SA lower affinity ((S)-[11C]rolipram) (n = 2) enantiomers were intravenously administered to Sprague-Dawley rats. Brain data were acquired using the ATLAS PET scanner and reconstructed using the 3D-ordered subset expectation maximization algorithm. Arterial samples were taken to measure unmetabolized [11C]rolipram. Total distribution volumes (VTâ²) were calculated using a 1-tissue compartment (1C) and an unconstrained 2-tissue compartment (2C) model. Results: High SA R experiments showed later and greater brain uptake, and slower washout than low SA R and S experiments. In all regions and in all experiments, the 2C model gave significantly better fitting than the 1C model. The poor fitting by the latter caused underestimation of VTâ² by 19-31%. The 2C model identified VTâ² reasonably well with coefficients of variation less than 10%. VTâ² values by this model were 16.4-29.2 mL/cm3 in high SA R, 2.9-3.5 in low SA R, and 3.1-3.7 in S experiments. Conclusions: Specific binding of (R)-[11C]rolipram was accurately measured in living rats. In high SA R experiments, â¼86% of VTâ² was specific binding. Distribution and changes of PDE4 in animal models can now be studied by measuring VTâ² of high SA (R)-[11C]rolipram.
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Authors
Masahiro Fujita, Sami S. Zoghbi, Matthew S. Crescenzo, Jinsoo Hong, John L. Musachio, Jian-Qiang Lu, Jeih-San Liow, Nicholas Seneca, Dnyanesh N. Tipre, Vanessa L. Cropley, Masao Imaizumi, Antony D. Gee, Jurgen Seidel, Michael V. Green, Victor W. Pike,