Quantification of brain phosphodiesterase 4 in rat with (R)-[11C]Rolipram-PET.
Fujita M,
Zoghbi SS,
Crescenzo MS,
Hong J,
Musachio JL,
Lu JQ,
Liow JS,
Seneca N,
Tipre DN,
Cropley VL,
Imaizumi M,
Gee AD,
Seidel J,
Green MV,
Pike VW,
Innis RB.
Molecular Imaging Branch, National Institute of Mental Health, Building 1, Room B3-10, 1 Center Drive, MSC-0135, Bethesda, MD 20892-0135, USA. FujitaM@intra.nimh.nih.gov
OBJECTIVE: Phosphodiesterase 4 (PDE4) catabolizes the second messenger 3', 5'-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)-[(11)C]rolipram) and high SA lower affinity ((S)-[(11)C]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 [(11)C]rolipram. Total distribution volumes (V(T)') 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 V(T)' by 19-31%. The 2C model identified V(T)' reasonably well with coefficients of variation less than 10%. V(T)' values by this model were 16.4-29.2 mL/cm(3) 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)-[(11)C]rolipram was accurately measured in living rats. In high SA R experiments, approximately 86% of V(T)' was specific binding. Distribution and changes of PDE4 in animal models can now be studied by measuring V(T)' of high SA (R)-[(11)C]rolipram.
PMID: 15961054 [PubMed - indexed for MEDLINE]