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Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.3/81525
- Quantification of brain phosphodiesterase 4 in rat with (R)-[11C] Rolipram-PET
- Fujita, Masahiro; Zoghbi, Sami S.; Crescenzo, Matthew S.; Hong, Jinsoo; Musachio, John L.; Lu, Jian-Qiang; Liow, Jeih-San; Seneca, Nicholas; Tipre, Dnyanesh N.; Cropley, Vanessa L.; Imaizumi, Masao; Gee, Antony D.; Seidel, Jurgen; Green, Michael V.; Pike, Victor W.; Innis, Robert B.
- 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)-[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 (VT′) 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 VT′ by 19–31%. The 2C model identified VT′ reasonably well with coefficients of variation less than 10%. VT′ 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, not, vert, similar86% of VT′ was specific binding. Distribution and changes of PDE4 in animal models can now be studied by measuring VT′ of high SA (R)-[11C]rolipram.
- Publication type
- Journal article
- NeuroImage, Vol. 26, no. 4 (Jul 2005), pp. 1201-1210
- Publication year
- FOR Code(s)
- 1103 Clinical Sciences; 1109 Neurosciences; 1702 Cognitive Sciences
- Cyclic adenosine monophosphate; Cyclic AMP; Pharmacokinetics; Phosphodiesterase 4; Plasma metabolites; Positron emission tomography; Rats; Rolipram; Small animal PET
- Publisher URL
- Copyright © 2005 Published by Elsevier Inc.
- Peer reviewed