A5016318094- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- Click Chemistry and Applications
- Advanced Neuroimaging Techniques and Applications
- Advanced MRI Techniques and Applications
- Psychedelics and Drug Studies
- Neurotransmitter Receptor Influence on Behavior
- Drug Transport and Resistance Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Chemical synthesis and alkaloids
- Neurological disorders and treatments
- Functional Brain Connectivity Studies
- Tryptophan and brain disorders
- Amino Acid Enzymes and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Proteomics Techniques and Applications
- Autophagy in Disease and Therapy
- Lanthanide and Transition Metal Complexes
- Adenosine and Purinergic Signaling
- Pulmonary Hypertension Research and Treatments
- Cardiac Imaging and Diagnostics
- Heat shock proteins research
University of Copenhagen
2020-2024
Copenhagen University Hospital
2020-2024
Rigshospitalet
2020-2024
Weatherford College
2024
Sage (United Kingdom)
2024
Biogen (United States)
2024
Lundbeck (Denmark)
2024
Aarhus University
2024
PureTech (United States)
2024
Yale University
2022-2024
A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT2AR) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but could linked to increased synaptogenesis down-regulation cerebral 5-HT2AR. Here, we investigate if psilocybin changes synaptic vesicle protein (SV2A) 5-HT2AR density in the pig brain. Twenty-four awake pigs received either 0.08 mg/kg or saline intravenously. Twelve (n = 6/intervention) were...
Pretargeting is a powerful nuclear imaging strategy to achieve enhanced contrast for nanomedicines and reduce the radiation burden healthy tissue. based on bioorthogonal chemistry. The most attractive reaction this purpose currently tetrazine ligation, which occurs between trans-cyclooctene (TCO) tags tetrazines (Tzs). Pretargeted beyond blood-brain barrier (BBB) challenging has not been reported thus far. In study, we developed Tz agents that are capable of ligating in vivo targets BBB. We...
Abstract Purpose 177 Lu-DOTATATE targeting the somatostatin receptor (SSTR) is utilized for treatment of neuroendocrine tumors (NETs). Onalespib, a heat shock protein 90 (HSP90) inhibitor, has demonstrated radiosensitizing properties and may thus enhance effect Lu-DOTATATE. Consequently, aim this study was to assess potential Onalespib in combination with vivo examine toxicity profiles treatments. Methods selectivity distribution NET xenografts were studied using biodistribution...
Parkinson's disease (PD) is caused by progressive neurodegeneration and characterised motor dysfunction. Neurodegeneration of dopaminergic neurons also causes aberrations within the cortico-striato-thalamo-cortical (CSTC) circuit, which has been hypothesised to lead non-motor symptoms such as depression. Individuals with PD have both lower synaptic density changes in neuronal metabolic function basal ganglia, measured using [11C]UCB-J [18F]FDG positron emission tomography (PET),...
A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT2AR) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but could linked to increased synaptogenesis down-regulation cerebral 5-HT2AR. Here, we investigate if psilocybin changes synaptic vesicle protein (SV2A) 5-HT2AR density in the pig brain. Twenty-four awake pigs received either 0.08 mg/kg or saline intravenously. Twelve (n=6/intervention) were...
Brain pretargeted nuclear imaging for the diagnosis of various neurodegenerative diseases is a quickly developing field. The tetrazine ligation currently most explored approach to achieve this goal due its remarkable properties. In work, we evaluated performance F-537-Tetrazine, previously developed by Biogen, and N-(3-[18F]fluoro-5-(1,2,4,5-tetrazin-3-yl)benzyl)propan-1-amine, in our group, thereby allowing direct comparison these two probes. evaluation included synthesis, radiolabeling...
Abstract Synaptic loss is a primary pathology in Alzheimer’s disease and correlates best with cognitive impairment as found post-mortem studies. Previously, we observed vivo reductions of synaptic density [11C]UCB-J PET (radiotracer for vesicle protein 2A) throughout the neocortex medial temporal brain regions early disease. In this study, applied independent component analysis to 2A-PET data identify networks associated deficits blinded data-driven manner. binding 2A was measured 38 (24...
Positron emission tomography (PET) is a molecular imaging technique that can be used to investigate the in vivo pharmacology of drugs. Initial preclinical evaluation PET tracers often conducted rodents due accessibility disease models as well economic considerations. Compared larger species, display higher expression and/or activity efflux transporters such P-glycoprotein (P-gp). Low brain uptake could, therefore, species-specific and not predictive for humans. We hypothesized better...
A positron emission tomography (PET) radiotracer to neuroimage α-synuclein aggregates would be a crucial addition for early diagnosis and treatment development in disorders such as Parkinson's disease, where elevated aggregate levels are histopathological hallmark. The (d3)-[11C]MODAG-001 has recently shown promise visualization of pre-formed fibrils (α-PFF) rodents. We here test the pig model proteins intracerebrally injected immediately before scanning. Four pigs were one hemisphere with...
Synapses are fundamental to the function of central nervous system and implicated in a number brain disorders. Despite their pivotal role, comprehensive imaging resource detailing distribution synapses human has been lacking until now. Here, we employ high-resolution PET neuroimaging healthy humans (17F/16M) create 3D atlas synaptic marker Synaptic Vesicle glycoprotein 2A (SV2A). Calibration absolute density values (pmol/ml) was achieved by leveraging postmortem autoradiography data. The...
The postsynaptic density (PSD) comprises numerous scaffolding proteins, receptors, and signaling molecules that coordinate synaptic transmission in the brain. Postsynaptic protein 95 (PSD-95) is a master scaffold within PSD one of its most abundant proteins therefore constitutes very attractive biomarker function pathological changes. Here, we exploit high-affinity inhibitor PSD-95, AVLX-144, as template for developing probes molecular imaging PSD. AVLX-144-based were labeled with...
The traditional design of PET target engagement studies is based on a baseline scan and one or more scans after drug administration. We here evaluate an alternative in which the administered during on-going (i.e., displacement study). This approach results both lower radiation exposure costs. Existing kinetic models assume steady state. condition not present consequently, our aim was to develop for analysing data. modified existing compartment accommodate time-variant increase occupancy...
Positron emission tomography (PET) has become an essential clinical tool for diagnosing neurodegenerative diseases with abnormal accumulation of proteins like amyloid-β or tau. Despite many attempts, it not been possible to develop appropriate radioligand imaging aggregated α-synuclein in the brain diagnosing, e.g., Parkinson’s Disease. Access a large animal model pathology would critically enable more translationally evaluation novel radioligands. We here establish pig cerebral injections...
Pretargeting is a powerful nuclear imaging strategy to achieve enhanced contrast for nanomedicines. It reduces the radiation burden healthy tissue. based on bioorthogonal chemistry. The most attractive reaction this purpose currently tetrazine ligation, which occurs between trans-cyclooctene (TCO) tags and tetrazines (Tzs). Pretargeted beyond blood-brain-barrier (BBB) has not been reported thus far. In study, we developed Tz agents that are capable ligate in vivo targets BBB. We chose...
Abstract Novel treatment strategies are needed to overcome some of the current challenges related resistance and latency within psychiatric field. Recently, psilocybin has shown promise as a novel major depressive disorder. A single dose is associated with lasting changes in personality mood. In parallel, various studies have indicated that microRNAs (miRNAs) regulated after antidepressive interventions. Here, pigs were used study transcriptional profiles miRNAs prefrontal cortex (PFC)...
<title>Abstract</title> <bold>Background: </bold>Alcohol consumption at clinically relevant doses alters brain glutamate release. However, few techniques exist to measure these changes in humans. The metabotropic receptor 5 (mGluR5) PET radioligand [<sup>11</sup>C]ABP688 is sensitive acute alcohol rodents, possibly mediated by effects on This study aimed determine the sensitivity of an challenge <bold>Methods:</bold> Eight social drinkers (25–42 years; females) with a recent drinking...
Parkinsons disease is a neurodegenerative disease, which associated with accumulation of α-synuclein protein aggregates and Lewy Body formation. These neurotoxic inclusions are especially harmful for dopamine-producing neurons in the substantia nigra brain. The cellular degradation system autophagy can reduce neurotoxicity caused by accumulated α-synuclein, targeting it degradation. Previously, we demonstrated that human TBC1D15 inhibits vitro, resulting aggregates. Conversely, lowering...
Abstract Positron emission tomography (PET) has become an essential clinical tool for diagnosing neurodegenerative diseases with abnormal accumulation of proteins like amyloid-β or tau. Despite many attempts, it not been possible to develop appropriate radioligand imaging aggregated α-synuclein in the brain diagnosing, e.g., Parkinson’s Disease. Access a large animal model pathology would critically enable more translationally evaluation novel radioligands. We here establish pig cerebral...
Abstract Background: A positron emission tomography (PET) radiotracer to neuroimage α-synuclein aggregates would be a crucial addition for early diagnosis and treatment development in disorders such as Parkinson's disease, where elevated aggregate levels is histopathological hallmark. The (d 3 )-[ 11 C]MODAG-001 has recently shown promise visualization of pre-formed fibrils (α-PFF) rodents. We here test the pig model proteins are intracerebrally injected immediately before scanning. Four...