Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.3/81525

Title

Quantification of brain phosphodiesterase 4 in rat with (R)-[11C] Rolipram-PET

Author(s)

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.

Abstract

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

Source

NeuroImage, Vol. 26, no. 4 (Jul 2005), pp. 1201-1210

Publication year

2005

FOR Code(s)

1103 Clinical Sciences;  1109 Neurosciences;  1702 Cognitive Sciences

Keyword(s)

Cyclic adenosine monophosphate;  Cyclic AMP;  Pharmacokinetics;  Phosphodiesterase 4;  Plasma metabolites;  Positron emission tomography;  Rats;  Rolipram;  Small animal PET

Publisher

Elsevier

ISSN

1053-8119

Publisher URL

http://dx.doi.org/10.1016/j.neuroimage.2005.03.017

Copyright

Copyright © 2005 Published by Elsevier Inc.

Peer reviewed