Psychobiological accounts of face processing predict that greater salience is attributed to faces matching a viewer's sexual preference than to faces that do not. However, behaviorally, this effect ...could only be demonstrated in tasks assessing reward ‘wanting’ (e.g. work-per-view-tasks) but not in tasks assessing ‘liking’ (e.g. facial attractiveness ratings), and has been found to be more pronounced in heterosexual men than women, especially with regard to very attractive faces. Here, we addressed the question if sex differences at the level of ‘wanting’ persist if participants are uninformed about the attractiveness of an anticipated male or female face. Seventeen heterosexual men and 13 heterosexual women (all single) participated in a social incentive delay task (SID). Participants were required to react on simple graphical cues in order to view a smiling face. Cues provided a priori information on the level of smile intensity (low/medium/high) as well as sex of the face (male/ female). A significant interaction of sex-of-face and sex-of-participant was observed in a priori defined regions of interest in the brain reward system (including ventral tegmental area, nucleus accumbens and ventromedial prefrontal cortex), reflecting enhanced activation to cues signaling opposite-sex faces relative to same-sex faces in both, men and women. Women additionally recruited the temporo-parietal junction (TPJ) during processing of opposite- vs. same-sex cues, suggesting stronger incorporation of social cognition processes in women than men. The findings speak against a general male bias for opposite-sex faces. Instead they provide preliminary evidence that men and women recruit different brain circuits during reward value assessment of facial stimuli.
► We probed reward valuation of opposite-sex faces in a social incentive delay task. ► Anticipating opposite-sex faces enhanced activation in the VTA, NAcc and vmPFC. ► No sex differences were observed in the brain reward circuit. ► Women differentially recruited TPJ during anticipation of male vs. female faces. ► Our data suggest sex differences in social cognition during face evaluation.
Objective:
Aripiprazole at clinically effective doses occupies some 90% of striatal dopamine 2 and 3 (D
2
D
3
) receptors. In order to further characterize its extrastriatal and time-dependent ...binding characteristics, the authors conducted positron emission tomography (PET) studies with the D
2
D
3
antagonist
18
Ffallypride at varying time points after the last aripiprazole administration in patients with schizophrenia.
Method:
Sixteen inpatients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder receiving treatment with aripiprazole underwent an
18
Ffallypride PET scan. Receptor occupancy was calculated as the percentage reduction in binding potential relative to unblocked values measured in eight age-matched, medication-free patients with schizophrenia. In addition, aripiprazole serum concentrations were determined as part of a routine therapeutic drug monitoring program in a large group of patients (N=128) treated with aripiprazole.
Results:
Mean dopamine D
2
D
3
receptor occupancy was high in all brain regions investigated, with no binding difference across brain regions. Nonlinear regression analysis revealed maximum attainable receptor occupancy (E
max
) values close to saturation. The values for serum concentration predicted to provide 50% of E
max
(EC
50
) were in the range of 5-10 ng ml in all brain regions. The D
2
D
3
receptors were completely saturated when serum aripiprazole concentration exceeded 100-150 ng ml. The mean concentration in the large clinical patient sample was 228 ng ml (SD=142).
Conclusions:
Because of its high affinity for D
2
D
3
receptors and its long elimination half-life, aripiprazole at clinical doses occupies a high fraction of its target receptor everywhere in the brain. Its dissociation from those receptors is very slow, such that the authors calculate from the results that in patients with serum aripiprazole concentrations in the range typical for clinical practice, D
2
D
3
receptors must remain nearly saturated for as long as 1 week after the last dose.
The voice is a marker of a person’s identity which allows individual recognition even if the person is not in sight. Listening to a voice also affords inferences about the speaker’s emotional state. ...Both these types of personal information are encoded in characteristic acoustic feature patterns analyzed within the auditory cortex. In the present study 16 volunteers listened to pairs of non-verbal voice stimuli with happy or sad valence in two different task conditions while event-related brain potentials (ERPs) were recorded. In an emotion matching task, participants indicated whether the expressed emotion of a target voice was congruent or incongruent with that of a (preceding) prime voice. In an identity matching task, participants indicated whether or not the prime and target voice belonged to the same person. Effects based on emotion expressed occurred earlier than those based on voice identity. Specifically, P2 (∼200ms)-amplitudes were reduced for happy voices when primed by happy voices. Identity match effects, by contrast, did not start until around 300ms. These results show an early task-specific emotion-based influence on the early stages of auditory sensory processing.
A better understanding of the factors underlying habitual tobacco smoking may further new strategies to go about this major health problem. The P300 event-related potential (ERP) has emerged as a ...valuable (endo)phenotype in neuropsychiatric research. Previous studies suggested the P300 ERP to be reduced in smokers. The main purpose of the present study was to provide an in-depth description of smoking-related behavioral, biological and electrophysiological phenotypes with an emphasis on the P300 ERP and its mutual relationship with other smoking-related parameters. In this case–control study N
=
1318 participants (smokers and never-smoking controls) were investigated at 6 German academic institutions. Study participants were randomly selected from the general population. Subjects with mental disorders including alcoholism and drug abuse were excluded. The main outcome measure was the P300 global field power (GFP). We found a lower P300 GFP in current smokers compared to never-smoking controls. Furthermore a correlation between measures of smoking severity and P300 GFP reduction was found. Non-addicted smokers exhibited normal P300 ERP measures. This study provides further evidence that the P300 ERP is reduced in current smokers even in the absence of potentially confounding psychiatric comorbidity. Thus, P300 amplitude reduction clearly is part of the electrophysiological phenotype of smokers. Our results provide the phenotypical groundwork for future multidimensional analyses of genotype–phenotype relationships in the field of smoking and nicotine dependence.
Lu-radiopharmaceuticals are routinely used for the treatment of various tumor entities. The productions of radiopharmaceuticals follow strict good-manufacturing practice guidelines and synthesis ...optimizations thereof have a strong impact on e.g. the quality of the product, radiation safety and costs. The purpose of this study is to optimize the precursor load of three radiopharmaceuticals. For that, different precursor loads were evaluated and compared to previously reported findings.
All three radiopharmaceuticals were successfully synthesized in high radiochemical purities and yields on the ML Eazy. The precursor load was optimized for
LuLu-FAPI-46 from 27.0 to 9.7 µg/GBq, for
LuLu-DOTATOC from 11 to 10 µg/GBq and for
LuLu-PSMA-I&T from 16.3 to 11.6 µg/GBq.
We successfully reduced the precursor load for all three radiopharmaceuticals while maintaining their quality.
Abstract Background 177Lu-radiopharmaceuticals are routinely used for the treatment of various tumor entities. The productions of radiopharmaceuticals follow strict good-manufacturing practice ...guidelines and synthesis optimizations thereof have a strong impact on e.g. the quality of the product, radiation safety and costs. The purpose of this study is to optimize the precursor load of three radiopharmaceuticals. For that, different precursor loads were evaluated and compared to previously reported findings. Results All three radiopharmaceuticals were successfully synthesized in high radiochemical purities and yields on the ML Eazy. The precursor load was optimized for 177LuLu-FAPI-46 from 27.0 to 9.7 µg/GBq, for 177LuLu-DOTATOC from 11 to 10 µg/GBq and for 177LuLu-PSMA-I&T from 16.3 to 11.6 µg/GBq. Conclusions We successfully reduced the precursor load for all three radiopharmaceuticals while maintaining their quality.
The controlled, self-assembled synthesis of multinuclear coordination compounds can be performed via different approaches. Frequently, steric, geometric and/or electronic factors located at the ...ligand systems predefine the way in which metal ions can assemble them to large aggregates. For the compounds in the present paper, also the Pearson’s acidities and preferred coordination geometries of the metal ions were used as organization principles. The ligand under study, 2,6-dipicolinoylbis(N,N-diethylthiourea), Hsub.2L1sup.ethyl, possesses ‘soft’ sulfur and ‘hard’ nitrogen and oxygen donors. One-pot reactions of this compound with AuCl(tht) (tht = tetrahydrothiophene) and Msup.3+ salts (M = Sc, Y, La, Ln, Ga, In) give products with gold-based {Ausub.3(L1sup.ethyl)sub.3}sup.3+ or {Ausub.2(L1sup.ethyl)sub.2}sup.2+ coronands, which host central Msup.3+ ions. The formation of such units is templated by the Msup.3+ ions and the individual size of the coronand rings is dependent on the ionic radii of the central ions in a way that small ions such as Gasup.3+ form a Ga⊂{Ausub.2(L1sup.ethyl)sub.2}sup.+ assembly, while larger ions (starting from Scsup.3+/Insup.3+) establish neutral M⊂{Ausub.3(L1sup.ethyl)sub.3} units with nine-coordinate central ions.
ABSTRACT
The aim of the present study was to examine neurocognitive function associated with chronic nicotine use. A total of 2163 healthy participants (1002 smokers, 1161 never‐smoking controls) ...participated in a population‐based case‐control design. The main outcome measures were six cognitive domain factors derived from a neuropsychological test battery. In smokers, the battery was administered after controlled smoking of one cigarette. Analyses included age, sex and education as covariates. Results demonstrated small, but significant deficits in smokers for visual attention (P < 0.001) and cognitive impulsivity (P < 0.006), while verbal episodic memory, verbal fluency, verbal working memory, and Stroop‐interference did not differ between groups. These attention/impulsivity deficits were also present in smokers with only a low amount of cigarette consumption. Lifetime nicotine use (pack‐years) was not correlated with cognition in smokers. In conclusion, this study confirmed subtle and specific cognitive deficits in non‐deprived smokers. The independence of these deficits from consumption intensity may argue for an a priori deficit of some cognitive abilities in smokers. These specific deficits may constitute intermediate phenotypes for genetic research on nicotine use.
Background
The radiometal gallium-68 (
68
Ga) is increasingly used in diagnostic positron emission tomography (PET), with
68
Ga-labeled radiopharmaceuticals developed as potential higher-resolution ...imaging alternatives to traditional
99m
Tc agents. In precision medicine, PET applications of
68
Ga are widespread, with
68
Ga radiolabeled to a variety of radiotracers that evaluate perfusion and organ function, and target specific biomarkers found on tumor lesions such as prostate-specific membrane antigen, somatostatin, fibroblast activation protein, bombesin, and melanocortin.
Main body
These
68
Ga radiopharmaceuticals include agents such as
68
GaGa-macroaggregated albumin for myocardial perfusion evaluation,
68
GaGa-PLED for assessing renal function,
68
GaGa-
t
-butyl-HBED for assessing liver function, and
68
GaGa-PSMA for tumor imaging. The short half-life, favourable nuclear decay properties, ease of radiolabeling, and convenient availability through germanium-68 (
68
Ge) generators and cyclotron production routes strongly positions
68
Ga for continued growth in clinical deployment. This progress motivates the development of a set of common guidelines and standards for the
68
Ga radiopharmaceutical community, and recommendations for centers interested in establishing
68
Ga radiopharmaceutical production.
Conclusion
This review outlines important aspects of
68
Ga radiopharmacy, including
68
Ga production routes using a
68
Ge/
68
Ga generator or medical cyclotron, standardized
68
Ga radiolabeling methods, quality control procedures for clinical
68
Ga radiopharmaceuticals, and suggested best practices for centers with established or upcoming
68
Ga radiopharmaceutical production. Finally, an outlook on
68
Ga radiopharmaceuticals is presented to highlight potential challenges and opportunities facing the community.
The molecular mechanisms of toxicity and cellular transport of anticancer metallodrugs, including platinum-based agents, have not yet been fully elucidated. The aim of our study was to investigate ...the relevance of copper transporters (CTR1 and ATP7A/B), organic cation transporters (OCT2) and the multidrug and toxin extrusion proteins (MATE) in the intracellular accumulation of a novel organometallic cytotoxic Au(III) compound in cancer cells in comparison to cisplatin. Specifically, the synthesis and characterization of the gold complex Au(py
-H)(PPh
Ar)ClPF
(PPh
Ar = 3-4-(diphenylphosphino)phenyl-7-methoxy-2H-chromen-2-one (
), featuring a coumarin ligand endowed with "smart" fluorescence properties, have been achieved. Initially, the cytotoxic effects of both cisplatin and
were studied in a small panel of human cancer cells, and against a non-tumorigenic cell line
. Thus, the human ovarian cancer cell line A2780 and its cisplatin resistant variant A2780cisR, were selected, being most sensitive to the treatment of the gold complex. Co-incubation of the metallodrugs with CuCl
(a CTR1 substrate) increased the cytotoxic effects of both the Au(III) complex and cisplatin; while co-incubation with cimetidine (inhibitor of OCT2 and MATE) showed some effect only after 72 h incubation. ICP-MS (Inductively Coupled Plasma Mass Spectrometry) analysis of the cell extracts showed that co-incubation with CuCl
increases Au and Cu accumulation in both cancer cell lines, in accordance with the enhanced antiproliferative effects. Conversely, for cisplatin, no increase in Pt content could be observed in both cell lines after co-incubation with either CuCl
or cimetidine, excluding the involvement of CTR1, OCT2, and MATE in drug accumulation and overall anticancer effects. This result, together with the evidence for increased Cu content in A2780 cells after cisplatin co-treatment with CuCl
, suggests that copper accumulation is the reason for the observed enhanced anticancer effects in this cell line. Moreover, metal uptake studies in the same cell lines indicate that both
and cisplatin are not transported intracellularly by CTR1 and OCT2. Finally, preliminary fluorescence microscopy studies enabled the visualization of the sub-cellular distribution of the gold compound in A2780 cells, suggesting accumulation in specific cytosolic components/organelles.
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