TY - JOUR T1 - Quantification of brain phosphodiesterase 4 using (<em>R</em>)-[C-11]rolipram in human and rhesus monkey JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 247P LP - 247P VL - 48 IS - supplement 2 AU - Masahiro Fujita AU - Sami Zoghbi AU - Yong Ryu AU - Jinsoo Hong AU - Robert Gladding AU - Victor Pike AU - Robert Innis Y1 - 2007/05/01 UR - http://jnm.snmjournals.org/content/48/supplement_2/247P.2.abstract N2 - 1145 Objectives: Rolipram binds to phosphodiesterase 4 (PDE4), the enzyme that catabolizes a major second messenger cAMP. (R)-[C-11]Rolipram has been successfully used to image brain PDE4 in rat, non-human primate, and human. The purposes of this study were to quantify (R)-[C-11]rolipram binding in rhesus monkey and human brain and examine the test-retest reproducibility of the measurements. Methods: Two monkey single scans and nine pairs of human test-retest (R)-[C-11]rolipram scans were performed with HRRT. Scans were performed for 2 h with the injection of ~185 and ~370 MBq in monkeys and humans, respectively. Arterial blood was sampled in all scans to measure metabolite-corrected arterial input function. Plasma free fraction (f1) was also measured in human scans. Distribution volume (V) was calculated in cortical and subcortical regions by one- (1C) and two-tissue compartment (2C) models. Results: As expected from postmortem studies, both monkey and human brain scans showed widespread distribution of (R)-[C-11]rolipram binding. Peak brain activity was 150-300% standard uptake value with higher levels in monkeys than in humans. Radioactivity represented by (R)-[C-11]rolipram in arterial plasma decreased to 50% in 10 and 75 min in monkeys and humans, respectively. In both species, 2C showed significantly better goodness-of-fit than 1C. 2C well identified V with ~5% COV and showed fairly uniform distribution in cortical and subcortical areas with average of 4.9 and 0.66 mL/cm3 in monkeys and humans, respectively. In humans, average V/f1 was 10 mL/cm3. Test-retest reproducibility was 16% and 21% for V/f1 and V, respectively in eight subjects while one subject who reported job-related stress at the time of one scan showed big variability of ~65%. Conclusions: V in human brain scans was consistent with the results of a previous study (Matthews JC, et al. J Cereb Blood Flow Metab 2003; 23:678) and smaller than in rats (Fujita M, et al. NeuroImage 2005; 26:1201) as expected from known binding site density. V/f1 showed modest reproducibility in most subjects. However, there may be confounding factors such as psychological stress. Better reproducibility of V/f1 than V indicates the necessity of measuring f1. Research Support (if any): NIMH Z01-MH-002795-04 ER -