Test-retest reproducibility of dopamine D2/3 receptor binding in human brain measured by PET with [11C]MNPA and [11C]raclopride.

PURPOSE: Dopamine D receptors (DRs) have two affinity states for endogenous dopamine, referred to as high-affinity state (D ), which has a high affinity for endogenous dopamine, and low-affinity state (D ). The density of D can be measured with (R)-2-CHO-N-n-propylnorapomorphine ([C]MNPA), while total density of D and D (DRs) can be measured with [C]raclopride using positron emission tomography (PET). Thus, the ratio of the binding potential (BP) of [C]MNPA to that of [C]raclopride ([C]MNPA/[C]raclopride) may reflect the proportion of the density of D to that of DRs. In the caudate and putamen, [C]MNPA/[C]raclopride reflects the proportion of the density of D to that of DRs. To evaluate the reliability of the PET paradigm with [C]MNPA and [C]raclopride, we investigated the test-retest reproducibility of non-displaceable BP (BP ) measured with [C]MNPA and of [C]MNPA/[C]raclopride in healthy humans. METHODS: Eleven healthy male volunteers underwent two sets of PET studies on separate days that each included [C]MNPA and [C]raclopride scans. BP values in the caudate and putamen were calculated. Test-retest reproducibility of BP of [C]MNPA and [C]MNPA/[C]raclopride was assessed by intra-subject variability (absolute variability) and test-retest reliability (intraclass correlation coefficient: ICC). RESULTS: The absolute variability of [C]MNPA BP was 5.30 ± 3.96 % and 12.3 ± 7.95 % and the ICC values of [C]MNPA BP were 0.72 and 0.82 in the caudate and putamen, respectively. The absolute variability of [C]MNPA/[C]raclopride was 6.11 ± 3.68 % and 11.60 ± 5.70 % and the ICC values of [C]MNPA/[C]raclopride were 0.79 and 0.80 in the caudate and putamen, respectively. CONCLUSION: In the present preliminary study, the test-retest reproducibility of BP of [C]MNPA and of [C]MNPA/[C]raclopride was reliable in the caudate and putamen.

Quantitative analysis of peripheral benzodiazepine receptor in the human brain using PET with (11)C-AC-5216.

UNLABELLED: Peripheral benzodiazepine receptor (PBR) is upregulated in activated glial cells and is therefore a useful biomarker for inflammation in the brain and neurodegenerative disorders. We developed a new PET radioligand, (11)C-AC-N-benzyl-N-ethyl-2-(7-methyl-8-oxo-2-pheyl-7,8-dihydro-9H-purin-9-yl)acetamide ((11)C-AC-5216), that allows the imaging and quantification of PBRs in monkey and mouse brains. The aim of this study was to evaluate a quantification method of (11)C-AC-5216 binding in the human brain. METHODS: A 90-min dynamic PET scan was obtained for each of 12 healthy men after an intravenous injection of (11)C-AC-5216. Regions of interest were drawn on several brain regions. Binding potential, compared with nondisplaceable uptake (BP(ND)), was calculated by a nonlinear least-squares fitting (NLS) method with the 2-tissue-compartment model, and total volume of distribution (V(T)) was estimated by NLS and graphical analysis methods. RESULTS: BP(ND) was highest in the thalamus (4.6 +/- 1.0) and lowest in the striatum (3.5 +/- 0.7). V(T) obtained by NLS or graphical analysis showed regional distribution similar to BP(ND). However, there was no correlation between BP(ND) and V(T) because of the interindividual variation of K(1)/k(2). BP(ND) obtained with data from a scan time of 60 min was in good agreement with that from a scan time of 90 min (r = 0.87). CONCLUSION: Regional distribution of (11)C-AC-5216 was in good agreement with previous PET studies of PBRs in the human brain. BP(ND) is more appropriate for estimating (11)C-AC-5216 binding than is V(T) because of the interindividual variation of K(1)/k(2). (11)C-AC-5216 is a promising PET ligand for quantifying PBR in the human brain.

The role of the uncinate fasciculus in memory and emotional recognition in amnestic mild cognitive impairment.

BACKGROUND: The putative neural bases of affected episodic memory and emotional recognition in early Alzheimer's disease are suspected to be limbic and paralimbic pathological processes. The uncinate fasciculus (UF) is especially considered to be a critical structure. In the present study, we investigated microstructural UF pathology by diffusion tensor imaging in the subjects with amnestic mild cognitive impairment (aMCI), and its association with memory and emotional processing impairment. METHODS: Subjects included 16 patients with aMCI and 16 healthy individuals. Diffusion tensor images were acquired and the fractional anisotropy (FA) of the UF was calculated. In addition, its association with verbal memory and emotional facial recognition was investigated. RESULTS: The FA values of the left UF were significantly lower in aMCI, and strongly correlated with episodic memory performance in aMCI. For the emotional recognition task, the aMCI subjects performed worse in negative emotion recognitions. The FA values of the left UF were correlated with the performance of fearful facial expression recognition in aMCI. CONCLUSION: These results indicated that microstructural alterations of the UF had already occurred in aMCI. In addition, these alterations could be one of the causes of memory and emotional processing impairment in aMCI.

Neural circuits in the brain that are activated when mitigating criminal sentences.

In sentencing guilty defendants, jurors and judges weigh 'mitigating circumstances', which create sympathy for a defendant. Here we use functional magnetic resonance imaging to measure neural activity in ordinary citizens who are potential jurors, as they decide on mitigation of punishment for murder. We found that sympathy activated regions associated with mentalising and moral conflict (dorsomedial prefrontal cortex, precuneus and temporo-parietal junction). Sentencing also activated precuneus and anterior cingulate cortex, suggesting that mitigation is based on negative affective responses to murder, sympathy for mitigating circumstances and cognitive control to choose numerical punishments. Individual differences on the inclination to mitigate, the sentence reduction per unit of judged sympathy, correlated with activity in the right middle insula, an area known to represent interoception of visceral states. These results could help the legal system understand how potential jurors actually decide, and contribute to growing knowledge about whether emotion and cognition are integrated sensibly in difficult judgments.

Quantification of dopamine transporter in human brain using PET with 18F-FE-PE2I.

UNLABELLED: (18)F-(E)-N-(3-iodoprop-2E-enyl)-2ß-carbofluoroethoxy-3ß-(4-methylphenyl)nortropane ((18)F-FE-PE2I) is a new PET radioligand with a high affinity and selectivity for the dopamine transporter (DAT). In nonhuman primates, (18)F-FE-PE2I showed faster kinetics and less production of radiometabolites that could potentially permeate the blood-brain barrier than did (11)C-PE2I. The aims of this study were to examine the quantification of DAT using (18)F-FE-PE2I and to assess the effect of radiometabolites of (18)F-FE-PE2I on the quantification in healthy humans. METHODS: A 90-min dynamic PET scan was obtained for 10 healthy men after intravenous injection of (18)F-FE-PE2I. Kinetic compartment model analysis with a metabolite-corrected arterial input function was performed. The effect of radiometabolites on the quantification was evaluated by time-stability analyses. The simplified reference tissue model (SRTM) method with the cerebellum as a reference region was evaluated as a noninvasive method of quantification. RESULTS: After the injection of (18)F-FE-PE2I, the whole-brain radioactivity showed a high peak (∼3-5 standardized uptake value) and fast washout. The radioactive uptake of (18)F-FE-PE2I in the brain was according to the relative density of the DAT (striatum > midbrain > thalamus). The cerebellum showed the lowest uptake. Tissue time-activity curves were well described by the 2-tissue-compartment model (TCM), as compared with the 1-TCM, for all subjects in all regions. Time stability analysis showed stable estimation of total distribution volume with 60-min or longer scan durations, indicating the small effect of radiometabolites. Binding potentials in the striatum and midbrain were well estimated by the SRTM method, with modest intersubject variability. Although the SRTM method yielded a slight underestimation and overestimation in regions with high and low DAT densities, respectively, binding potentials by the SRTM method were well correlated to the estimates by the indirect kinetic method with 2-TCM. CONCLUSION: (18)F-FE-PE2I is a promising PET radioligand for quantifying DAT. The binding potentials could be reliably estimated in both the striatum and midbrain using both the indirect kinetic and SRTM methods with a scan duration of 60 min. Although radiometabolites of (18)F-FE-PE2I in plasma possibly introduced some effects on the radioactivity in the brain, the effects on estimated binding potential were likely to be small.