3BP-3940, a highly potent FAP-targeting peptide for theranostics - production, validation and first in human experience with Ga-68 and Lu-177.

Hardly any new tracers attracted more attention in nuclear medicine in the last couple of years than radiolabeled fibroblast activation protein inhibitors (FAPi'). Molecules targeting cancer-associated fibroblasts (CAFs) or disease-associated fibroblasts in benign disorders (DAFs) gave rise to a new class of radiopharmaceuticals widely applicable for imaging and with the desired use as therapeutic compounds. Despite displaying benefits in diagnostic sensitivity over FDG, most FAP-targeting compounds in today's clinical routine continue to lack therapeutic utility due to short tumor retention.

From Automated Synthesis to In Vivo Application in Multiple Types of Cancer-Clinical Results with [Ga]Ga-DATA.SA.FAPi.

Radiolabeled FAPI (fibroblast activation protein inhibitors) recently gained attention as widely applicable imaging and potential therapeutic compounds targeting CAF (cancer-associated fibroblasts) or DAF (disease-associated fibroblasts in benign disorders). Moreover, the use of FAPI has distinct advantages compared to FDG (e.g.

Computational studies, design and synthesis of Pd(II)-based complexes: Allosteric inhibitors of the Human Topoisomerase-IIα.

Herein, a robust docking protocol was developed by using a low-cost workflow to highlight the modulation at ATPase domain from Human Topoisomerase-IIα (TOP2A) towards four novel Pd(II)-complexes bearing N,S-donor ligands. In vitro TOP2A inhibition assay confirmed the ability of them to prevent the enzyme functions into concentration ranging at 6.25-25μM.

Low Malignancy Rates in Fine-Needle Aspiration Cytologies in a Primary Care Setting in Germany.

Background: Reported results for thyroid nodule fine-needle aspiration (FNA) cytology mainly originate from tertiary centers. However, thyroid nodule FNA cytology is mainly performed in primary care settings for which the distribution of FNA Bethesda categories and their respective malignancy rates are largely unknown. Therefore, this study investigated FNA cytology malignancy rates of a large primary care setting to determine to what extent current evidence-based strategies for the malignancy risk stratification of thyroid nodules are applied and applicable in such primary care settings.

Crystal structure of -ethyl-2-(1,2,3,4-tetra-hydro-naphthalen-1-yl-idene)hydrazinecarbo-thio-amide.

There are two crystallographically independent mol-ecules in the asymmetric unit of the title compound, CHNS, one of them being disordered over the methyl group [site-occupancy ratio = 0.705 (5):0.295 (5)].

Evaluation of a Two-Year Routine Application of Molecular Testing of Thyroid Fine-Needle Aspirations Using a Seven-Gene Panel in a Primary Referral Setting in Germany.

Background: Major differences with respect to the diagnostic performance of a "ruling in" approach in the presurgical diagnosis of indeterminate thyroid fine-needle aspirations (FNAs) have been reported. Therefore, the aim of this prospective multicenter study was to investigate the specific diagnostic impact of mutation testing using a seven-gene panel in a routine primary referral setting analyzing FNAs from endocrinology and nuclear medicine practices in Germany.

Methods: RNA and DNA was extracted from 564 routine air-dried FNA smears obtained from 64 physicians and cytologically graded by one experienced cytopathologist.

Crystal structure of 4-hy-droxy-3-meth-oxy-benzaldehyde 4-methyl-thio-semi-carbazone methanol monosolvate.

In the title solvate, C15H15N3O2S·CH3OH, the thio-semicarbazone mol-ecule is approximately planar; the maximum deviation from the mean plane is 0.4659 (14) Å and the dihedral angle between the aromatic rings is 9.83 (8)°.

Crystal structure of (E)-2-[4-(4-hy-droxy-phen-yl)butan-2-yl-idene]hydrazine-1-carbo-thio-amide.

The title compound, C11H15N3OS, is a thio-semicarbazone derivative of the raspberry ketone rheosmin [systematic name: 4-(4-hy-droxy-phen-yl)butane-2-one]. The mol-ecule deviates from planarity, with the bridging C-C-C=N torsion angle equal to -101.3 (2)°.

Dopamine D2/D3 receptor availability and venturesomeness.

The construct of impulsivity is considered as a major trait of personality. There is growing evidence that the mesolimbic dopamine system plays an important role in the modulation of impulsivity and venturesomeness, the two key components within the impulsivity-construct. The aim of the present study was to explore an association between trait impulsivity measured with self-assessment and the dopaminergic neurotransmission as measured by positron emission tomography (PET) in a cohort of healthy male subjects.

Importance of 123I-metaiodobenzylguanidine scintigraphy/single photon emission computed tomography for diagnosis and differential diagnostics of Parkinson syndromes.

The goal of Parkinson syndrome diagnostics is twofold: early diagnosis on the one hand, and accurate differentiation among idiopathic and atypical Parkinson syndromes on the other. (123)I-metaiodobenzylguanidine scintigraphy is the only method that can distinguish with a high degree of sensitivity and specificity between atypical Parkinson syndromes and Parkinson's disease or dementia with Lewy bodies. Additional advantages are the method's widespread availability and radioactive exposure dose comparable to that for single photon emission computed tomography imaging with much lower costs.

Alteration of dopamine D2/D3 receptor binding in patients with juvenile myoclonic epilepsy.

Purpose: To quantify extrastriatal and striatal D2/D3 receptor binding in patients with juvenile myoclonic epilepsy (JME) using the high-affinity dopamine D2/D3 receptor positron emission tomography (PET) ligand (18) F-Fallypride ([(18) F]FP).

Methods: Twelve patients with JME and 21 age-matched control subjects were studied. Dynamic images (180 min) were acquired after injection of [(18) F]FP.

Human dopamine receptor D2/D3 availability predicts amygdala reactivity to unpleasant stimuli.

Dopamine (DA) modulates the response of the amygdala. However, the relation between dopaminergic neurotransmission in striatal and extrastriatal brain regions and amygdala reactivity to affective stimuli has not yet been established. To address this issue, we measured DA D2/D3 receptor (DRD2/3) availability in twenty-eight healthy men (nicotine-dependent smokers and never-smokers) using positron emission tomography with [18F]fallypride.

In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy.

Purpose: Alterations in dopamine neurotransmission in animal models of epilepsies have been frequently demonstrated using invasive neuroscience or ex vivo techniques. We aimed to test whether corresponding alterations could be detected by noninvasive in vivo brain imaging with positron emission tomography (PET) in the chronic phase of the rat pilocarpine model of temporal lobe epilepsy.

Methods: Six pilocarpine-treated Wistar rats exhibiting spontaneous recurrent seizures and nine control rats were studied with PET using [(18)F]-fallypride, a high-affinity dopamine D(2/3) receptor ligand.

Striatal and extrastriatal D2/D3-receptor-binding properties of ziprasidone: a positron emission tomography study with [18F]Fallypride and [11C]raclopride (D2/D3-receptor occupancy of ziprasidone).

To elucidate the "atypicality" of ziprasidone, its striatal and extrastriatal D2/D3-receptor binding was characterized in patients with schizophrenia under steady-state conditions. These data were compared with striatal receptor occupancy values after single-dose ziprasidone ingestion in healthy controls. [F]fallypride positron emission tomography (PET) recordings were obtained in 15 patients under steady-state ziprasidone treatment at varying time points after the last dose.

Choice of reference area in studies of Alzheimer's disease using positron emission tomography with fluorodeoxyglucose-F18.

At present, there is still no consensus on the choice of the reference area in positron emission tomography (PET) studies of Alzheimer's disease (AD). In this study, PET scans with fluorodeoxyglucose-F18 were carried out in the following groups of subjects: 47 patients with probable AD, 8 patients with mild cognitive impairment, and 15 age-similar healthy subjects. Scans normalized to the cerebral global mean (CGM), cerebellum (CBL), and the primary sensorimotor cortex (SMC).

Association of low striatal dopamine d2 receptor availability with nicotine dependence similar to that seen with other drugs of abuse.

Objective: All drugs of abuse induce a phasic dopamine release within the striatum that does not undergo habituation. Prolonged substance consumption impairs the natural function of the mesolimbic dopamine system, as shown by a decrease in the availability of striatal dopamine 2 (D(2)) receptors in patients suffering from cocaine, heroin, amphetamine, and alcohol dependence. However, it is unclear whether similar changes can also be observed in heavy-smoking nicotine-dependent smokers.

Reduced cerebral fluoro-L-dopamine uptake in adult patients suffering from phenylketonuria.

Deficiency of phenylalanine hydroxylase activity in phenylketonuria (PKU) causes an excess of phenylalanine (Phe) throughout the body, predicting impaired synthesis of catecholamines in the brain. To test this hypothesis, we used positron emission tomography (PET) to measure the utilization of 6-[18F]fluoro-L-DOPA [corrected] (FDOPA) in the brain of adult patients suffering from PKU and in healthy controls. Dynamic 2-h long FDOPA emission recordings were obtained in seven adult PKU patients (five females, two males; age: 21 to 27 years) with elevated serum Phe levels, but lacking neurologic deficits.

Tiagabine does not attenuate alcohol-induced activation of the human reward system.

Rationale: The rewarding effects of ethanol and other drugs of abuse are mediated by activation of the mesolimbic dopamine system. Recent neuroimaging studies in primates and humans suggest that cocaine-induced dopamine stimulation might be diminished by drugs augmenting gamma-aminobutyric acid A (GABA-A) receptor function such as the GABA transaminase inhibitor vigabatrin.

Objectives: The objective of this study was to test the property of the selective GABA transporter 1 (GAT1) inhibitor tiagabine to block ethanol-induced activation of the mesolimbic reward system in an i.

Decreased dopamine D2/D3-receptor binding in temporal lobe epilepsy: an [18F]fallypride PET study.

Purpose: Although animal data are suggestive, evidence for an alteration of the extrastriatal dopaminergic system in human focal epilepsy is missing.

Methods: To quantify D2/D3-receptor density, we studied seven patients with temporal lobe epilepsy (TLE) and nine age-matched controls with positron emission tomography (PET) by using the high-affinity dopamine D2/D3-receptor ligand [18F]Fallypride ([18F]FP) suitable for imaging extrastriatal binding. TLE was defined by interictal and ictal video-EEG, magnetic resonance imaging (MRI), and [18F]fluorodeoxyglucose ([18F]FDG)-PET and was due to hippocampal sclerosis (HS), based on histology in all patients.

The striatal and extrastriatal D2/D3 receptor-binding profile of clozapine in patients with schizophrenia.

Positron emission tomography (PET) studies reveal that clozapine at clinically used doses occupies less than 60% of D2/D3 dopamine receptors in human striatum. Here, the occupancy of D2/D3 dopamine receptors by clozapine in patients with schizophrenia was determined to test the hypothesis that clozapine binds preferentially to extrastriatal dopamine receptors. A total of 15 clozapine-treated inpatients with schizophrenia underwent a [18F]fallypride PET scan.

Parametric mapping of binding in human brain of D2 receptor ligands of different affinities.

Unlabelled: (11)C-Raclopride has been widely used for PET studies of dopamine D(2/3) receptors in human brain. The long half-life of (18)F may impart advantages to the novel moderate-affinity benzamide (18)F-desmethoxyfallypride and its high-affinity congener (18)F-fallypride for competition studies and for detection of extrastriatal binding. However, the in vivo kinetics of these compounds and the quantification approaches for parametric mapping of their specific bindings have not been systematically compared.

Acute alcohol effects on neuronal and attentional processing: striatal reward system and inhibitory sensory interactions under acute ethanol challenge.

The acute influence of ethanol on cerebral activity induces complex psycho-physiological effects that are considerably more pronounced during acute ethanol influx than during maximal blood alcohol concentration (elimination phase). Despite the psychiatric and forensic relevance of these different ethanol effects, the underlying neuronal mechanisms are still unclear. In total, 20 male healthy volunteers were investigated each with three different experimental conditions in a randomized order using an intravenous ethanol challenge (40 g bolus infusion): during influx phase, elimination phase, and under placebo condition.