PET Whole Body Biodistribution and Test Retest Brain Imaging Studies Using a Phosphodiesterase 4 Inhibitor (R)-[11C]Rolipram

Both basic and clinical studies have indicated that the 3', 5'-cyclic adenosine monophosphate (cAMP) system plays critical roles in several brain diseases, particularly in mood disorders and drug addiction. cAMP is synthesized from adenosine 5'-triphosphate (ATP) by adenylyl cyclase and metabolized by cyclic nucleotide phosphodiesterases (PDEs). Among components of the cAMP pathway, PDE4 appears to be critical for antidepressant effects. 4-[3-(cyclopentoxyl)-4-methoxyphenyl]-2-pyrrolidone (rolipram) is an inhibitor of PDE4. As a positron emission tomography (PET) brain imaging agent, rolipram has good properties such as high affinity of 1-2 nM and appropriate lipophilicity (Log P) of ~3. A rat study gave an estimation of low radiation absorbed doses of the active enantiomer (R)-[11C]rolipram. ciociWEge quality. Therefore, R-[11C]rolipram is a promising PET ligand. However, radiation absorbed doses have not been estimated from human whole body imaging studies and a method to measure binding of (R)-[11C]rolipram in human brain has not been established.

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The purposes of this protocol are to estimate radiation absorbed doses of (R)-[11C]rolipram by performing whole body imaging studies on healthy human subjects and also to establish an accurate method to measure PDE4 levels in brain by performing test retest brain imaging studies. The results of this overall study are required to apply this PET ligand in various neurological and psychiatric disorders in the future.