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Imaging cAMP-specific phosphodiesterase-4 in human brain with R-[11C]rolipram and positron emission tomography

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Abstract.

Evidence of disruptions in cAMP-mediated signaling in several neuropsychiatric disorders has led to the development of R-[11C]rolipram for imaging phosphodiesterase-4 (PDE4) enzymes with positron emission tomography (PET). The high-affinity PDE4 inhibitor rolipram was previously reported to have an antidepressant effect in humans. PDE4 is abundant in the brain, and it hydrolyzes cAMP produced following stimulation of various neurotransmitter systems. PDE4 is regulated by intracellular cAMP levels. This paper presents the first PET study of R-[11C]rolipram in living human brain. Consistent with the wide distribution of PDE4, high radioactivity retention was observed in all regions representing the gray matter. Rapid metabolism was observed, and kinetic analysis demonstrated that the data fit in a two-tissue compartment model. R-[11C]Rolipram is thus suitable for imaging PDE4 and possibly cAMP signal transduction in the living human brain with PET.

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Authors and Affiliations

  1. PET Centre, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario, Canada, M5T 1R8, , , , ,

    Jean N. DaSilva, Celia M. Lourenco, Jeffrey H. Meyer, Douglas Hussey & Sylvain Houle

  2. Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, USA, , , , ,

    William Z. Potter

Authors
  1. Jean N. DaSilva
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  2. Celia M. Lourenco
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  3. Jeffrey H. Meyer
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  4. Douglas Hussey
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  5. William Z. Potter
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  6. Sylvain Houle
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DaSilva, J.N., Lourenco, C.M., Meyer, J.H. et al. Imaging cAMP-specific phosphodiesterase-4 in human brain with R-[11C]rolipram and positron emission tomography. Eur J Nucl Med 29, 1680–1683 (2002). https://doi.org/10.1007/s00259-002-0950-y

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  • DOI: https://doi.org/10.1007/s00259-002-0950-y

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