An analysis of the CatWalk XT and a composite score to assess neurofunctional deficits after photothrombosis in mice.

The purpose of this study was to evaluate CatWalk's capability for assessing the functional outcome after photothrombotic stroke affecting the motor cortex of mice. Mice were tested up to 21 days after photothrombosis or sham surgery using CatWalk, and a composite score assessing functional deficits (neuroscore). The neuroscore demonstrated deficits of the contralateral forelimb for more than two weeks after stroke.

Towards chronic deep brain stimulation in freely moving hemiparkinsonian rats: applicability and functionality of a fully implantable stimulation system.

This study aimed at investigating a novel fully implantable deep brain stimulation (DBS) system and its ability to modulate brain metabolism and behavior through subthalamic nucleus (STN) stimulation in a hemiparkinsonian rat model.Twelve male rats were unilaterally lesioned with 6-hydroxydopamine in the medial forebrain bundle and received a fully implantable DBS system aiming at the ipsilesional STN. Each rat underwent three cylinder tests to analyze front paw use: a PRE test before any surgical intervention, an OFF test after surgery but before stimulation onset and an ON test under DBS.

Circulatory dipeptidyl peptidase 3 (cDPP3) is a potential biomarker for early detection of secondary brain injury after aneurysmal subarachnoid hemorrhage.

Introduction: Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) that can culminate in secondary brain damage. Although it remains one of the main preventable causes of aSAH-related morbidity, there is still a lack of prognostic criteria for identification of patients at risk of developing DCI. Because elevated circulatory levels of the enzyme dipeptidyl peptidase 3 (cDPP3) were recently identified as a potential biomarker for outcome prediction in critically ill patients, we evaluated the time-course of changes in cDPP3 levels after aSAH.

Design, synthesis and biological evaluation of Tozadenant analogues as adenosine A receptor ligands.

With the aim to obtain potent adenosine A receptor (AR) ligands, a series of eighteen derivatives of 4-hydroxy-N-(4-methoxy-7-morpholin-4-yl-1,3-benzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide (SYN-115, Tozadenant) were designed and synthesized. The target compounds were obtained by a chemical building block principle that involved reaction of the appropriate aminobenzothiazole phenyl carbamates with either commercially available or readily synthesized functionalized piperidines. Their affinity and subtype selectivity with regard to human adenosine A-and A receptors were determined using radioligand binding assays.

Nuclear Medicine in Times of COVID-19: How Radiopharmaceuticals Could Help to Fight the Current and Future Pandemics.

The emergence and global spread of COVID-19, an infectious disease caused by the novel coronavirus SARS-CoV-2, has resulted in a continuing pandemic threat to global health. Nuclear medicine techniques can be used for functional imaging of (patho)physiological processes at the cellular or molecular level and for treatment approaches based on targeted delivery of therapeutic radionuclides. Ongoing development of radiolabeling methods has significantly improved the accessibility of radiopharmaceuticals for in vivo molecular imaging or targeted radionuclide therapy, but their use for biosafety threats such as SARS-CoV-2 is restricted by the contagious nature of these agents.

Ca2.3 channel function and Zn-induced modulation: potential mechanisms and (patho)physiological relevance.

Voltage-gated calcium channels (VGCCs) are critical for Ca influx into all types of excitable cells, but their exact function is still poorly understood. Recent reconstruction of homology models for all human VGCCs at atomic resolution provides the opportunity for a structure-based discussion of VGCC function and novel insights into the mechanisms underlying Ca selective flux through these channels. In the present review, we use these data as a basis to examine the structure, function, and Zn-induced modulation of Ca2.

[F]-JK-PSMA-7 PET/CT Under Androgen Deprivation Therapy in Advanced Prostate Cancer.

Purpose: PSMA imaging is frequently used for monitoring of androgen deprivation therapy (ADT) in prostate cancer. In a previous study, [F]-JK-PSMA-7 exhibited favorable properties for tumor localization after biochemical recurrence. In this retrospective study, we evaluated the performance of [F]-JK-PSMA-7 under ADT.

Dnmt3a2/Dnmt3L Overexpression in the Dopaminergic System of Mice Increases Exercise Behavior through Signaling Changes in the Hypothalamus.

Dnmt3a2, a DNA methyltransferase, is induced by neuronal activity and participates in long-term memory formation with the increased expression of synaptic plasticity genes. We wanted to determine if Dnmt3a2 with its partner Dnmt3L may influence motor behavior via the dopaminergic system. To this end, we generated a mouse line, Dnmt3a2/3L, with dopamine transporter (DAT) promotor driven Dnmt3a2/3L overexpression.

Development and Evaluation of a Versatile Receptor-Ligand Binding Assay Using Cell Membrane Preparations Embedded in an Agarose Gel Matrix and Evaluation with the Human Adenosine A Receptor.

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Radiosynthesis and evaluation of F-labeled dopamine D-receptor ligands.

Introduction: The dopamine D receptor (DR) has attracted considerable attention as potential target for the treatment of a broad range of central nervous system disorders. Although many efforts have been made to improve the performance of putative radioligand candidates, there is still a lack of DR selective tracers suitable for in vivo PET imaging. Thus, the objective of this work was to develop a D-selective PET ligand for clinical applications.

Preparation of labeled aromatic amino acids via late-stage F-fluorination of chiral nickel and copper complexes.

A general protocol for the preparation of 18F-labeled AAAs and α-methyl-AAAs applying alcohol-enhanced Cu-mediated radiofluorination of Bpin-substituted chiral complexes using Ni/Cu-BPX templates as double protecting groups is reported. The chiral auxiliaries are easily accessible from commercially available starting materials in a few synthetic steps. The versatility of the method was demonstrated by the high-yielding preparation of a series of [18F]F-AAAs and the successful implementation of the protocol into automated radiosynthesis modules.

One-Stop Shop: F-Flortaucipir PET Differentiates Amyloid-Positive and -Negative Forms of Neurodegenerative Diseases.

Tau protein aggregations are a hallmark of amyloid-associated Alzheimer disease and some forms of non-amyloid-associated frontotemporal lobar degeneration. In recent years, several tracers for in vivo tau imaging have been under evaluation. This study investigated the ability of F-flortaucipir PET not only to assess tau positivity but also to differentiate between amyloid-positive and -negative forms of neurodegeneration on the basis of different F-flortaucipir PET signatures.

Preparation of a First F-Labeled Agonist for M Muscarinic Acetylcholine Receptors.

M muscarinic acetylcholine receptors (mAChRs) are abundant in postsynaptic nerve terminals of all forebrain regions and have been implicated in the cognitive decline associated with Alzheimer's disease and other CNS pathologies. Consequently, major efforts have been spent in the development of subtype-selective positron emission tomography (PET) tracers for mAChRs resulting in the development of several C-labeled probes. However, protocols for the preparation of F-labeled mAChR-ligands have not been published so far.

Positron Emission Tomography Imaging of Long-Term Expression of the 18 kDa Translocator Protein After Sudden Cardiac Arrest in Rats.

Background: Knowledge about the neuroinflammatory state during months after sudden cardiac arrest is scarce. Neuroinflammation is mediated by cells that express the 18 kDa translocator protein (TSPO). We determined the time course of TSPO-expressing cells in a rat model of sudden cardiac arrest using longitudinal in vivo positron emission tomography (PET) imaging with the TSPO-specific tracer [18F]DAA1106 over a period of 6 months.

Chronic Psychosocial Stress Causes Increased Anxiety-Like Behavior and Alters Endocannabinoid Levels in the Brain of C57Bl/6J Mice.

Chronic stress causes a variety of physiological and behavioral alterations, including social impairments, altered endocrine function, and an increased risk for psychiatric disorders. Thereby, social stress is one of the most effective stressful stimuli among mammals and considered to be one of the major risk factors for the onset and progression of neuropsychiatric diseases. For analyzing the effects of social stress in mice, the resident/intruder paradigm of social defeat is a widely used model.

Early-phase [F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury.

Purpose: Second-generation tau radiotracers for use with positron emission tomography (PET) have been developed for visualization of tau deposits in vivo. For several β-amyloid and first-generation tau-PET radiotracers, it has been shown that early-phase images can be used as a surrogate of neuronal injury. Therefore, we investigated the performance of early acquisitions of the novel tau-PET radiotracer [F]PI-2620 as a potential substitute for [F]fluorodeoxyglucose ([F]FDG).

Cannabinoids and the endocannabinoid system in anxiety, depression, and dysregulation of emotion in humans.

Purpose Of Review: This review is to summarize most recent evidence published in the last 18 months on medical and recreational use of cannabis and cannabinoids in relation to anxiety, depression (unipolar and bipolar), and dysregulation of emotions as part of posttraumatic stress disorders (PTSD) and emotionally instable personality disorders. It also covers the investigation of endocannabinoids as potential biomarkers in these conditions. This is important with increasing medicinal use of cannabinoids and growing social tolerance towards recreational cannabis use.

Intraindividual Comparison of F-PSMA-1007 with Renally Excreted PSMA Ligands for PSMA PET Imaging in Patients with Relapsed Prostate Cancer.

F-prostate-specific membrane antigen (PSMA)-1007 is excreted mainly through the liver. We benchmarked the performance of F-PSMA-1007 against 3 renally excreted PSMA tracers. Among 668 patients, we selected 27 in whom PET/CT results obtained with Ga-PSMA-11, F-DCFPyL (2-(3-(1-carboxy-5-[(6-[F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid), or F-JK-PSMA-7 (JK, Juelich-Koeln) were interpreted as equivocal or negative or as oligometastatic disease (PET-1).

Alcohol-Supported Cu-Mediated F-Fluorination of Iodonium Salts under "Minimalist" Conditions.

In the era of personalized precision medicine, positron emission tomography (PET) and related hybrid methods like PET/CT and PET/MRI gain recognition as indispensable tools of clinical diagnostics. A broader implementation of these imaging modalities in clinical routine is closely dependent on the increased availability of established and emerging PET-tracers, which in turn could be accessible by the development of simple, reliable, and efficient radiolabeling procedures. A further requirement is a GMP production of imaging probes in automated synthesis modules.

Biodistribution and radiation dosimetry of [F]-JK-PSMA-7 as a novel prostate-specific membrane antigen-specific ligand for PET/CT imaging of prostate cancer.

Aim: We investigated the whole-body distribution and the radiation dosimetry of [F]-JK-PSMA-7, a novel F-labeled PSMA-ligand for PET/CT imaging of prostate cancer.

Methods: Ten patients with prostate cancer and biochemical recurrence or radiologic evidence of metastatic diseases were examined with 329-384 MBq (mean 359 ± 17 MBq) [F]-JK-PSMA-7. Eight sequential positron emission tomography (PET) scans were acquired from 20 min to 3 h after injection with IRB approval.

An F-Labeled PSMA Ligand for PET/CT of Prostate Cancer: First-in-Humans Observational Study and Clinical Experience with F-JK-PSMA-7 During the First Year of Application.

In preclinical trials, the recently developed tracer 2-methoxy-F-DCFPyL (F-JK-prostate-specific membrane antigen [PSMA]-7) has shown favorable properties regarding clinical performance and radiochemical accessibility. The aim of this study was to evaluate the clinical utility of F-JK-PSMA-7 for PET/CT imaging of patients with prostate cancer. In an Institutional Review Board-approved pilot study, the initial clinical utility of PET/CT imaging with F-JK-PSMA-7 was directly compared with Ga-PSMA-11 PET/CT in a group of 10 patients with prostate cancer.

Peripheral ganglia in healthy rats as target structures for the evaluation of PSMA imaging agents.

Background: The recent implementation of PET with prostate specific membrane antigen (PSMA)-specific radiotracers into the clinical practice has resulted in the significant improvement of accuracy in the detection of prostate carcinoma (PCa). PSMA-expression in ganglia has been regarded as an important pitfall in prostate carcinoma-PET diagnostics but has not found any practical use for diagnosis or therapy.

Methods: We explored this phenomenon and demonstrated the applicability of peripheral ganglia in healthy rats as surrogates for small PSMA positive lesions for the preclinical evaluation of diagnostic PCa PET probes.

Level of education mitigates the impact of tau pathology on neuronal function.

Purpose: Using PET imaging in a group of patients with Alzheimer's disease (AD), we investigated whether level of education, a proxy for resilience, mitigates the harmful impact of tau pathology on neuronal function.

Methods: We included 38 patients with mild-to-moderate AD (mean age 67 ± 7 years, mean MMSE score 24 ± 4, mean years of education 14 ± 4; 20 men, 18 women) in whom a [F]AV-1451 scan (a measure of tau pathology) and an [F]FDG scan (a measure of neuronal function) were available. The preprocessed PET scans were z-transformed using templates for [F]AV-1451 and [F]FDG from healthy controls, and subsequently thresholded at a z-score of ≥3.

Minimalist approach meets green chemistry: Synthesis of F- labeled (hetero)aromatics in pure ethanol.

The application of toxic solvents and additives is inevitable for most of the described protocols for F-labeling. Herein, a novel "green" procedure for nucleophilic aromatic radiofluorination of highly activated (hetero)aromatic substrates in pure EtOH is described. Using this method a series of F-labeled (hetero)arenes have been synthesized in radiochemical yields (RCYs) of up to 97%.

Effects of subthalamic deep brain stimulation on striatal metabolic connectivity in a rat hemiparkinsonian model.

Deep brain stimulation (DBS) in the subthalamic nucleus (STN) has been successfully used for the treatment of advanced Parkinson's disease, although the underlying mechanisms are complex and not well understood. There are conflicting results about the effects of STN-DBS on neuronal activity of the striatum, and its impact on functional striatal connectivity is entirely unknown. We therefore investigated how STN-DBS changes cerebral metabolic activity in general and striatal connectivity in particular.