
Bernd NeumaierUniversity of Cologne | UOC · Institute of Radiochemistry and Experimental Molecular Imaging
Bernd Neumaier
Prof. Dr.
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456
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Introduction
Additional affiliations
January 2015 - present
March 2013 - present
University Clinic Cologne, Germany
Position
- Managing Director
October 2006 - February 2013
Publications
Publications (456)
Purpose
In addition to rodent models, the chick embryo model has gained attention for radiotracer evaluation. Previous studies have investigated tumours on the chorioallantoic membrane (CAM), but its value for radiotracer imaging of intracerebral tumours has yet to be demonstrated.
Procedures
Human U87 glioblastoma cells and U87-IDH1 mutant glioma...
Background: The radiotracer [18F]JK-PSMA-7, a prostate cancer imaging agent for positron emission tomography (PET), was previously synthesized by indirect radiofluorination using an 18F-labeled active ester as a prosthetic group, which had to be isolated and purified before it could be linked to the pharmacologically active Lys-urea-Glu motif. Alth...
Dysfunctions in autophagy, a cellular mechanism for breaking down components within lysosomes, often lead to neurodegeneration. The specific mechanisms underlying neuronal vulnerability due to autophagy dysfunction remain elusive. Here we show that autophagy contributes to cerebellar Purkinje cell (PC) survival by safeguarding their glycolytic acti...
Background
In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinct biodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In this study, we aime...
In animal studies it has been observed that the inhibitory neuromodulator adenosine is released into the cerebral interstitial space during hypoxic challenges. Adenosine's actions on the A1 adenosine receptor (A1AR) protect the brain from oxygen deprivation and overexertion through adjustments in cerebral blood flow, metabolism, and electric activi...
Purpose: In addition to rodent models, the chick embryo model has gained attention for radiotracer evaluation. Previous studies investigated tumours on the chorioallantoic membrane (CAM), but its value for radiotracer imaging of intracerebral tumours has not yet been demonstrated. Procedures: Human U87 glioblastoma cells and U87-IDH1 mutant glioma...
Mutations of isocitrate dehydrogenase 1 (IDH1) are key biomarkers for glioma classification, but current methods for detection of mutated IDH1 (mIDH1) require invasive tissue sampling and cannot be used for longitudinal studies. Positron emission tomography (PET) imaging with mIDH1-selective radioligands is a promising alternative approach that cou...
Compensatory changes in brain connectivity keep motor symptoms mild in prodromal Parkinson’s disease. Studying compensation in patients is hampered by the steady progression of the disease and a lack of individual baseline controls. Furthermore, combining fMRI with walking is intricate. We therefore used a seed-based metabolic connectivity analysis...
Nuclear reaction cross sections for the formation of ⁷²As and ⁷¹As in proton-induced reactions on enriched ⁷²Ge targets were measured up to 45 MeV utilizing three different cyclotrons at the Forschungszentrum Jülich. The stacked-thin sample activation technique in combination with high-resolution γ-ray spectrometry was used. The major γ-ray peaks o...
Plain Language Summary
In a study of 32 patients with progressive supranuclear palsy (PSP), we used a molecular imaging tracer called [¹⁸F]PI-2620 to measure two things: the presence of a protein called tau in deep brain areas (specifically, the globus pallidus internus and dentate nucleus) and the function of the brain’s cortex by assessing blood...
Excitation functions of the $$^{86}$$ 86 Sr(d,n) $$^{87m,87g}$$ 87 m , 87 g Y, $$^{86}$$ 86 Sr(d,2n) $$^{86m,86g}$$ 86 m , 86 g Y and $$^{86}$$ 86 Sr(d,3n) $$^{85m,85g}$$ 85 m , 85 g Y reactions on enriched $$^{86}$$ 86 Sr target were measured by the activation technique up to deuteron energies of 49 MeV. The isomeric cross-section ratios as a func...
Introduction:
Radionuclide therapy using 177Lu-labeled prostate-specific membrane antigen (PSMA) ligands is an established treatment option for patients with PSMA-positive metastatic castration-resistant prostate cancer. Prior to radionuclide therapy, theranostics require identification of appropriate patients by PSMA-PET. [68Ga]Ga-PSMA-11 has ofte...
Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired performance caused by insufficient sleep. It is unclear (1) whether daily use of caffeine could prevent or exacerbate the GM alterations induced by 5-day sleep restriction (i.e. chro...
O-([18F]Fluoroethyl)-l-tyrosine ([18F]FET) is actively transported into the brain and cancer cells by LAT1 and possibly other amino acid transporters, which enables brain tumor imaging by positron emission tomography (PET). However, tumor delivery of this probe in the presence of competing amino acids may be limited by a relatively low affinity for...
Background and objectives:
Clinical heterogeneity of patients with Parkinson disease (PD) is well recognized. PD with REM sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher nonmotor symptom burden. However, the neural mechanisms underlying this clinical divergence concerning imbalances in neurotran...
Degeneration of dopaminergic neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinson’s disease. In idiopathic cases, high levels of mitochondrial DNA alterations, leading to mitochondrial dysfunction, are a central feature of these vulnerable neurons.
Here we present a mouse model expressing the...
We used a new data-driven methodology to identify a set of reference regions that enhanced the quantification of the SUV ratio of the second-generation tau tracer 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([18F]PI-2620) in a group of patients clinically diagnosed with 4-repeat tauopathy, specifically progressive supranuclea...
Imaging of the A1 adenosine receptor (A1R) by positron emission tomography (PET) with 8-cyclopentyl-3-(3-[18F]fluoropropyl)-1-propyl-xanthine ([18F]CPFPX) has been widely used in preclinical and clinical studies. However, this radioligand suffers from rapid peripheral metabolism and subsequent accumulation of radiometabolites in the vascular compar...
Tozadenant (4-hydroxy-N-(4-methoxy-7-morpholinobenzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide) is a highly selective adenosine A2A receptor (A2AR) antagonist and a promising lead structure for the development of A2AR-selective positron emission tomography (PET) probes. Although several 18F-labelled tozadenant derivatives showed favorable in...
Access to SuFExable compounds was remarkably simplified by introduction of the solid FO2S-donor SuFEx-IT. However, the published process for preparation of this reagent relies on the use of sulfuryl fluoride (SO2F2), which is difficult to obtain and highly toxic. Herein, we disclose a simple protocol for SO2F2-free, hectogram-scale preparation of t...
Dysfunctions in autophagy, a cellular mechanism for breaking down components within lysosomes, often lead to neurodegeneration. The specific mechanisms underlying neuronal vulnerability to autophagy dysfunction remain elusive. Here, we show that autophagy contributes to the survival of cerebellar Purkinje cells (PCs) by safeguarding their glycolyti...
Ti exhibits favorable decay properties for positron emission tomography (PET) imaging and can be easily produced by the bombardment of natural scandium (Sc) by protons using the ⁴⁵ Sc(p,n) ⁴⁵ Ti nuclear reaction. However, separation of ⁴⁵ Ti from irradiated Sc targets is arduous due to the hydrolytic instability of Ti(IV) complexes, making it a sig...
Background
Alzheimer’s disease (AD) is characterized by the cerebral accumulation of amyloid‐beta (A), tau (T), and progressive neurodegeneration (N). The widely used ATN system, with regard to positron emission tomography (PET) biomarkers, categorizes AD based on the mean signal in specific regions of interest (ROI). However, this procedure disreg...
Background and Objective
Anti-IgLON5 disease is a recently discovered neurological disorder combining autoimmunity and neurodegeneration. Core manifestations include sleep disorders, bulbar symptoms and gait abnormalities followed by cognitive dysfunction, but other presentations have been reported. Hallmarks are autoantibodies targeting the neuron...
Tryptophan (Trp) is an essential proteinogenic amino acid and metabolic precursor for several signaling molecules that has been implicated in many physiological and pathological processes. Since the two main branches of Trp metabolism—serotonin biosynthesis and kynurenine pathway—are differently affected by a variety of neurological and neoplastic...
Morphological imaging using MRI is essential for brain tumour diagnostics. Dynamic susceptibility contrast (DSC) perfusion-weighted MRI (PWI), as well as amino acid PET, may provide additional information in ambiguous cases. Since PWI is often unavailable in patients referred for amino acid PET, we explored whether maps of relative cerebral blood v...
Copper has several clinically relevant radioisotopes and versatile coordination chemistry, allowing attachment of its radionuclides to biological molecules. This characteristic makes it suitable for applications in molecular imaging or radionuclide targeted therapy. Of particular interest in nuclear medicine today is the theranostic approach. This...
Introduction
The fMRI BOLD response to emotional stimuli highlighting the role of the medial prefrontal cortex (MPFC) has been thoroughly investigated. Recently, the relationship between emotion processing and GABA levels has been studied using MPFC proton magnetic resonance spectroscopy (1H-MRS). However, the role of GABAA receptors in the MPFC du...
Background
The TgF344-AD ratline represents a transgenic animal model of Alzheimer’s disease. We previously reported spatial memory impairment in TgF344-AD rats, yet the underlying mechanism remained unknown. We, therefore, set out to determine if spatial memory impairment in TgF344-AD rats is attributed to spatial disorientation. Also, we aimed to...
18F-Fluorination of sensitive molecules is often challenging, but can be accomplished under suitably mild conditions using radiofluorinated prosthetic groups (PGs). Herein, 1-alkylamino-7-[18F]fluoro-8-azaisatoic anhydrides ([18F]AFAs) are introduced as versatile 18F-labeled building blocks that can be used as amine-reactive or "click chemistry" PG...
BACKGROUND
The TgF344-AD ratline represents a transgenic animal model of Alzheimer’s disease (AD). We previously reported spatial memory impairment in TgF344-AD rats, yet the underlying mechanism remained unknown. We, therefore, set out to determine if spatial memory impairment in TgF344-AD rats is attributed to spatial disorientation. Also, we aim...
Accurate assessment of isolated radiochemical yields (RCYs) is a prerequisite for efficient and reliable optimization of labeling reactions. In practice, radiochemical conversions (RCCs) determined by HPLC analysis of crude reaction mixtures are often used to estimate RCYs. However, incomplete recovery of radioactivity from the stationary phase can...
The EEG alpha rhythm (∼ 8-13 Hz) is one of the most salient human brain activity rhythms, modulated by the level of attention and vigilance and related to cerebral energy metabolism. Spectral power in the alpha range in wakefulness and sleep strongly varies among individuals based on genetic predisposition. Knowledge about the underlying genes is s...
Evidence has shown that both sleep loss and daily caffeine intake can induce changes in grey matter (GM). Caffeine is frequently used to combat sleepiness and impaired performance caused by insufficient sleep. It is unclear 1) whether daily use of caffeine could prevent or exacerbate the GM alterations induced by chronic sleep restriction, and 2) w...
Identifying ligands targeting G protein coupled receptors (GPCRs) with novel chemotypes other than the physiological ligands is a challenge for in silico screening campaigns. Here we present an approach that identifies novel chemotype ligands by combining structural data with a random forest agonist/antagonist classifier and a signal-transduction k...
Degeneration of dopamine neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinson's disease (PD). In idiopathic cases, high levels of mitochondrial DNA (mtDNA) mutations associated with mitochondrial dysfunction are a central feature of these vulnerable neurons. Here we present a mouse model expr...
The β⁺- emitting radionuclide ⁸⁶gY (t1/2 = 14.7 h) forms a matched-pair with the β⁻-emitting therapeutic radionuclide ⁹⁰Y (t1/2 = 2.7 d) for theranostic application in medicine. Precise knowledge of the positron emission probability of the PET nuclide is very important, which was rather uncertain for 86gY until recently. In this work, an 86gY sourc...
The accumulation of tau is a hallmark of several neurodegenerative diseases and is associated with neuronal hypoactivity and presynaptic dysfunction. Oral administration of the adenosine A1 receptor antagonist rolofylline (KW-3902) has previously been shown to reverse spatial memory deficits and to normalize the basic synaptic transmission in a mou...
Background: Morphological imaging using MRI is essential for brain tumour diagnostics. Dynamic susceptibility contrast (DSC) perfusion-weighted MRI (PWI), as well as amino acid PET, may provide additional information in ambiguous cases. Since PWI is not always performed as part of standard MRI in brain tumours, we explored whether maps of relative...
Identifying the correct chemotype of ligands targeting receptors (i.e., agonist or antagonist) is a challenge for in silico screening campaigns. Here we present an approach that identifies novel chemotype ligands by combining structural data with a random forest agonist/antagonist classifier and a signal-transduction kinetic model. As a test case,...
Gliomas are the most common primary brain tumors in adults. A diffuse infiltrative growth pattern and high resistance to therapy make them largely incurable, but there are significant differences in the prognosis of patients with different subtypes of glioma. Mutations in isocitrate dehydrogenase (IDH) have been recognized as an important biomarker...
The EEG alpha rhythm (8-13 Hz) is one of the most salient human brain activity rhythms. Spectral power in the alpha range in wakefulness and sleep varies among individuals based on genetical predisposition, yet knowledge about the underlying genes is scarce. The EEG alpha oscillations are related to cerebral energy metabolism and modulated by the l...
Positron emission tomography (PET) imaging with radiotracers that bind to fibrillary amyloid β (Aβ) deposits is an important tool for the diagnosis of Alzheimer's disease (AD) and for the recruitment of patients into clinical trials. However, it has been suggested that rather than the fibrillary amyloid β (Aβ) deposits, it is smaller, soluble Aβ ag...
Background and Objectives
Clinical heterogeneity of patients with Parkinson’s disease is well recognized. Parkinson’s disease with rapid eye movement (REM) sleep behavior disorder (RBD) is a more malignant phenotype with faster motor progression and higher non-motor symptom burden. However, the neural mechanisms underlying this clinical divergence...
4‐repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R‐tauopathies are progressive‐supranuclear‐palsy (PSP) and corticobasal‐syndrome (CBS) characterized by tau accumulation in subcortical nuclei as well as cortical neuronal dysfunction, as shown by PET‐assessed hyp...
4‐repeat (4R) tauopathies are neurodegenerative diseases characterized by cerebral accumulation of 4R tau pathology. The most prominent 4R‐tauopathies are progressive‐supranuclear‐palsy (PSP) and corticobasal‐syndrome (CBS) characterized by tau accumulation in subcortical nuclei as well as cortical neuronal dysfunction, as shown by PET‐assessed hyp...
Cross sections of the ⁸⁶ Sr(p,3n) 84m Y, ⁸⁶ Sr(p,αn) 82m Rb, and ⁸⁶ Sr(p,x) 85g Sr reactions were measured from their respective thresholds up to 16.2 MeV and from 23.0 to 44.1 MeV at FZJ, and from 14.3 to 24.5 MeV at LBNL, using 96.4% enriched ⁸⁶ SrCO 3 as target material. Thin targets prepared by sedimentation were irradiated with protons in a st...
Cu‐mediated radiofluorination is a versatile tool for the preparation of ¹⁸F‐labeled (hetero)aromatics. In this work, we systematically evaluated a series of complexes and identified several generally applicable mediators for highly efficient radiofluorination of aryl boronic and stannyl substrates. Utilization of these mediators in nBuOH/DMI or DM...
Einleitung: Die Beeinträchtigung der kognitiven Leistung durch Schlafmangel kann bei verschiedenen Personen unterschiedlich stark sein. In Studien, die akuten Schlafentzug untersuchten, zeigte sich ein Zusammenhang zwischen der Verfügbarkeit der A1 Adenosin-Rezeptoren (A1AR) im Gehirn und der kognitiven Leistung. Fragestellung: Wir untersuchten nun...
Background:
Transcranial direct current stimulation (tDCS) promotes recovery after stroke in humans. The underlying mechanisms, however, remain to be elucidated. Animal models suggest tDCS effects on neuroinflammation, stem cell proliferation, neurogenesis, and neural plasticity.
Objective:
In a longitudinal study, we employed tDCS in the subacu...
Purpose
Early after [ ¹⁸ F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [ ¹⁸ F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease...
Brains are among the most energetically costly tissues in the mammalian body.¹ This is predominantly caused by expensive neurons with high glucose demands.² Across mammals, the neuronal energy budget appears to be fixed, possibly posing an evolutionary constraint on brain growth.3, 4, 5, 6 Compared to similarly sized mammals, birds have higher numb...
Objectives/Introduction: Studies on acute sleep deprivation have linked the individual vulnerability to sleep-loss induced performance impairments to the cerebral adenosinergic regulation. Here we aimed at investigating the impact of chronic sleep restriction on this system. Methods: Thirty-six volunteers followed a protocol of 3 baseline nights (8...