NIMH DIRP MIB - Recent Findings

Background. . In addition to imaging membrane bound receptors, PET can measure proteins involved in second messenger systems. [¹¹C]rolipram is a high affinity probe for cAMP phosphodiesterase-4, the enzyme that metabolizes cAMP. Rolipram has active (R) and inactive (S) forms. These slide show enantiomeric selectivity of uptake such that the active isomer is retained in brain, whereas the inactive is not. In addition, addition of nonradioactive compound is able to block uptake of (R)-rolipram, showing that this site is saturable. The cAMP cascade is thought to be upregulated by antidepressant medications. We are now using (R)-[¹¹C]rolipram in human subjects to compare depressed patients and healthy subjects and to study the effects of chronic antidepressant treatment.

Legend. Coronal slices in the same location of high SA (R), low SA (R), and high SA (S)-[¹¹C]rolipram PET experiments at 0 - 11, 20 - 40, and 50 - 80 min. All images are spatially normalized to the standard space. Integrated images during the three time periods are shown. Compared to low SA R and high SA S experiments, the high SA R experiments showed greater activity, slower washout, and more heterogeneous distribution of activity. Because the level of activities was different among the three studies, different color scales are used.

References. 1.) M. Fujita, S.S. Zoghbi, M.S. Crescenzo, J. Hong, J.L. Musachio, J.Q. Lu, J.-S. Liow, N.Seneca, D.N. Tipre, V.L. Cropley, M. Imaizumi, A.D. Gee, J. Seidel, M.V. Green, V.W. Pike, and R.B. Innis. Quantification of brain phosphodiesterase 4 in rat with (R)-[¹¹C]rolipram-PET. NeuroImage. 26: 1201-1210, 2005.
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2) M. Fujita, M. Imaizumi, C. D'Sa, S.S. Zoghbi, M.S. Crescenzo, J. Hong, J.L. Musachio, A.D. Gee, J. Seidel, M.V. Green, V.W. Pike, R.S. Duman, and R.B. Innis In vivo and in vitro measurement of brain phosphodiesterase 4 in rats after antidepressant treatment, Synapse, 61: 78-86, 2007. Download Reference in PDF Format (434 kb)

3)T. Itoh, K. Abe, S.S. Zoghbi, O. Inoue, J. Hong, M. Imaizumi, V.W. Pike, R.B. Innis, and M. Fujita. Positron emission tomographic measurement of the in vivo affinity of ¹¹C-(R)-rolipram and the density of its target, phosphodiesterase-4, in brain of conscious and anesthetized rats. J. Nucl. Med., 50: 749-756, 2009. Download Reference in PDF Format (468 kb)