Regions of interest (ROI).

<p>(A) Sagittal image of regional radioactivity after intravenous injection of [¹¹C]FLB 457 in one subject. Thalamic ROI. (B) Coronal image of regional radioactivity after intravenous injection of [¹¹C]raclopride. Striatal ROI.</p

Partial correlations between regional D2 receptor binding potential, divergent thinking and intelligence, controlling for age.

<p>*Significant at p≤0.017, corrected for multiple comparisons (n = 3) using an <i>α</i> = 0.05.</p>a<p>One-tailed <i>p</i>-value (direction of correlation according to hypothesis). Other values are two-tailed.</p><p>Raven  =  Raven's Standard Progressive Matrices Plus scores; BIS  =  Berliner Intelligenz Struktur Test scores; Thalamus  =  Dopamine D2 receptor binding potential (D2BP) in the thalamus; Striatum  =  D2BP in the striatum; FC  =  D2BP in the frontal cortex.</p

Additional file 1: of [11C]SCH23390 binding to the D1-dopamine receptor in the human brain—a comparison of manual and automated methods for image analysis

Table S1. Mean BPND values of [11C]SCH23390 in the morning and afternoon, the absolute variability, and ICC in 15 healthy men in four brain regions. There are eight BPND values for each region derived from the different combinations of methods in the analysis process. (DOCX 18 kb

Correlations between SocDes and PhTA scores and ROI BPND from the previous [9] and present study.

<p>The table also displays the replication BFs which denotes how much support there is for a successful replication, by quantifying how much evidence there is in favor of the original correlation compared to no correlation. Note that the correlation between PhTA and STR was not significant in the original study but have still been included here for completeness.</p

Relationships between D1-R BP_ND in striatum and social desirability and physical trait aggression.

<p>The dotted lines indicate the 95% confidence intervals. Raw scale scores have been transformed to T-scores for illustrative purposes in this figure.</p

D1-R BP_ND map and regions of interest.

<p>The top row displays an average D1-R BP_ND brain map of all subjects. The middle row shows the whole-striatum ROI (red). The bottom row shows the limbic striatum ROI (yellow) used in this replication study.</p

Prior and posterior distributions underlying the replication Bayes factors.

<p>In each graph the dotted line denotes the prior which is determined by the correlation from the original study. The posterior (solid line) is obtained by updating the prior using the correlation from the present study. The Savage-Dickey Ratio (the ratio between the heights of the two dots) is then used to calculate the Bayes factor in favor of the original correlation over the null-hypothesis of no correlation. See Verhagen & Wagenmakers [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0193770#pone.0193770.ref014" target="_blank">14</a>] for a full explanation of this procedure. In this study, data support the null hypothesis over the original correlations and the Bayes factors hence signifies failed replications.</p

Discovery and Preclinical Validation of [¹¹C]AZ13153556, a Novel Probe for the Histamine Type 3 Receptor

The histamine type 3 receptor (H₃) is a G protein-coupled receptor implicated in several disorders of the central nervous system. Herein, we describe the radiolabeling and preclinical evaluation of a candidate radioligand for the H₃ receptor, 4-(1<i>S</i>,2<i>S</i>)-2-(4-cyclobutylpiperazine-1-carbonyl)­cyclopropyl]-<i>N</i>-methyl-benzamide (<b>5</b>), and its comparison with one of the frontrunner radioligands for H₃ imaging, namely, GSK189254 (<b>1</b>). Compounds <b>1</b> and <b>5</b> were radiolabeled with tritium and carbon-11 for in vitro and in vivo imaging experiments. The in vitro binding of [³H]<b>1</b> and [³H]<b>5</b> was examined by (i) saturation binding to rat and nonhuman primate brain tissue homogenate and (ii) in vitro autoradiography on tissue sections from rat, guinea pig, and human brain. The in vivo binding of [¹¹C]<b>1</b> and [¹¹C]<b>5</b> was examined by PET imaging in mice and nonhuman primates. <i>B</i>_max values obtained from Scatchard analysis of [³H]<b>1</b> and [³H]<b>5</b> binding were in good agreement. Autoradiography with [³H]<b>5</b> on rat, guinea pig, and human brain slices showed specific binding in regions known to be enhanced in H₃ receptors, a high degree of colocalization with [³H]<b>1</b>, and virtually negligible nonspecific binding in tissue. PET measurements in mice and nonhuman primates demonstrated that [¹¹C]<b>5</b> binds specifically and reversibly to H₃ receptors in vivo with low nonspecific binding in brain tissue. Whereas [¹¹C]<b>1</b> showed similar binding characteristics in vivo, the binding kinetics appeared faster for [¹¹C]<b>5</b> than for [¹¹C]<b>1</b>. Conclusions: [¹¹C]<b>5</b> has suitable properties for quantification of H₃ receptors in nonhuman primate brain and has the potential to offer improved binding kinetics in man compared to [¹¹C]<b>1</b>