Figure 1.

Positron emission tomography measurement of ¹¹C-(R)-rolipram binding. To measure ¹¹C-(R)-rolipram binding in brain as well as metabolism and clearance of the radioligand in plasma, both regional brain (A) and blood (B) data were acquired for 90 minutes; this included data before and well after the peak. Unmetabolized levels of ¹¹C-(R)-rolipram (open symbols in [B]) were measured in arterial plasma in each scan by radio high-performance liquid chromatography. High-performance liquid chromatography separated the unmetabolized ¹¹C-(R)-rolipram and radiometabolites and enabled measurement of the unmetabolized radioligand levels. Tri-exponential fitting (solid line in [B]) was performed for unmetabolized ¹¹C-(R)-rolipram. From this tri-exponentially fitted curve and brain data (open symbols in [A]), an unconstrained two-compartment model provided the fitted curve (solid line in [A]) and gave total distribution volume (V_T). V_T was normalized to plasma free fraction (f_P) measured by ultrafiltration. These V_T/f_P values in the 10 regions were compared between control subjects and subjects with major depressive disorder. In addition, ¹¹C-(R)-rolipram binding levels (V_T/f_P) were calculated in each volume element (i.e., voxel) of the images by Logan plot (C) to compare groups in each voxel using Statistical Parametric Mapping (Figure S1 in Supplement 1). The representative data shown here were obtained from a 26-year old male patient with major depressive disorder. Conc, concentration; SUV, standard uptake value.