A5069406575- Click Chemistry and Applications
- Radiopharmaceutical Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- Medical Imaging Techniques and Applications
- Phenothiazines and Benzothiazines Synthesis and Activities
- Chemical Reactions and Isotopes
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Synthesis and Biological Evaluation
- Parkinson's Disease Mechanisms and Treatments
- Pharmacological Receptor Mechanisms and Effects
- Analytical Chemistry and Chromatography
- HER2/EGFR in Cancer Research
- Alzheimer's disease research and treatments
- Crystallization and Solubility Studies
- Neuropeptides and Animal Physiology
- Advanced biosensing and bioanalysis techniques
- X-ray Diffraction in Crystallography
- Synthesis and biological activity
- Molecular spectroscopy and chirality
- Peptidase Inhibition and Analysis
- Quinazolinone synthesis and applications
- bioluminescence and chemiluminescence research
- Chemical Reaction Mechanisms
University of Copenhagen
2020-2025
TetraPlan
2024
KTH Royal Institute of Technology
2023-2024
Science for Life Laboratory
2023-2024
University of Gothenburg
2022-2024
University of Modena and Reggio Emilia
2010-2022
Virginia Commonwealth University
2015-2021
Azienda Unita' Sanitaria Locale Di Modena
2016
The development of highly selective and fast biocompatible reactions for ligation cleavage has paved the way new diagnostic therapeutic applications pretargeted in vivo chemistry. concept bioorthogonal pretargeting attracted considerable interest, particular targeted delivery radionuclides drugs. In nuclear medicine, can provide increased target-to-background ratios at early time-points compared to traditional approaches. This reduces radiation burden healthy tissue and, depending on...
A simple, scalable and reliable direct 18 F-labeling procedure has been developed applied to obtain a pretargeting tetrazine-based imaging agent with favorable in vivo characteristics.
Pretargeted PET imaging is an emerging and fast-developing method to monitor immuno-oncology strategies. Currently, tetrazine ligation considered the most promising bioorthogonal reaction for pretargeting in vivo. Recently, we have developed a 18F-label ultrareactive tetrazines by copper-mediated fluorinations. However, bispyridyl tetrazines-one of structures vivo pretargeted applications-were inaccessible using this strategy. We believed that our successful efforts H-tetrazines low basic...
Abstract Introduction Cannabis sativa L. is a powerful medicinal plant and its use has recently increased for the treatment of several pathologies. Nonetheless, side effects, like dizziness hallucinations, long‐term effects concerning memory cognition, can occur. Most alarming lack standardised procedure to extract cannabis. Indeed, each galenical preparation an unknown chemical composition in terms cannabinoids other active principles that depends on extraction procedure. Objective This...
Pretargeted imaging of nanomedicines have attracted considerable interest because it has the potential to increase contrast while reducing radiation burden healthy tissue. Currently, tetrazine ligation is fastest bioorthogonal reaction for this strategy and, consequently, state-of-art choice in vivo chemistry. We recently identified key properties tetrazines pretargeting. also developed a method 18F-label reactive using an aliphatic nucleophilic substitution strategy. Here, we combined...
Pretargeted radioimmunoimaging has been shown to enhance tumor-to-background ratios by up 125-fold at early time points, leading more efficient and less toxic radionuclide therapies, particularly with shorter half-lives such as astatine-211 (211At). The tetrazine ligation is the most utilized bioorthogonal reaction in these strategies, making tetrazines ideal for 211At labeling controlling biodistribution. We developed a 211At-labeled pretargeting agent alpha-radionuclide therapy, achieving...
Pretargeted imaging harnessing tetrazine ligation has gained increased interest over recent years. Targeting vectors with slow pharmacokinetics may be visualized using short-lived radionuclides, such as fluorine-18 (18F) for positron emission tomography (PET), and result in improved target-to-background ratios compared to conventionally radiolabeled slowly accumulating vectors. We recently developed different radiochemical protocols enabling the direct radiofluorination of various scaffolds,...
Tetrazines (Tz) have been applied as bioorthogonal agents for various biomedical applications, including pretargeted imaging approaches. In radioimmunoimaging, pretargeting increases the target-to-background ratio while simultaneously reducing radiation burden. We recently reported a strategy to directly 18F-label highly reactive tetrazines based on 3-(3-fluorophenyl)-Tz core structure. Herein, we report kinetic study this versatile scaffold. A library of 40 different was prepared, fully...
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...
Liver pyruvate kinase (PKL) has recently emerged as a new target for non-alcoholic fatty liver disease (NAFLD), and inhibitors of this enzyme could represent therapeutic option. However, breakthrough is complicated by selectivity issues since exists in four different isoforms. In work, we report that ellagic acid (EA) its derivatives, present numerous fruits vegetables, can inhibit PKL potently selectively. Several polyphenolic analogues EA were synthesized tested to identify the chemical...
Aliphatic nucleophilic substitution (SN2) with [18F]fluoride is the most widely applied method to prepare 18F-labeled positron emission tomography (PET) tracers. Strong basic conditions commonly used during 18F-labeling procedures inherently limit or prohibit labeling of base-sensitive scaffolds. The high basicity stems from tradition trap on anion exchange cartridges and elute it afterward anions. This sequence facilitate transfer an aqueous aprotic organic, polar reaction medium, which...
Abstract A set of 211 At‐astatoarenes were synthesized from corresponding trimethylgermyl arenes with an average radiochemical conversion (RCC) ca. 50 % for electron‐rich and approx. 70 in case electron‐deficient arenes. Both electron rich poor substrates successfully radiolabeled at room temperature (RT) using relatively low precursor amounts (0.15 μmol/0.02 mL solvent (7.5 mM)). Ready access to ortho‐, para‐ meta‐ astatinated was achievable. Optimized reaction conditions applied label a...
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...
Radiolabeling of tetrazines has gained increasing attention due to their important role in pretargeted imaging or therapy. The most commonly used radionuclide PET is fluorine-18. For this reason, we have recently developed a method which enables the direct aromatic 18F-fluorination using stannane precursors through copper-mediated fluorinations. Herein, further optimized labeling procedure. 3-(3-fluorophenyl)-1,2,4,5-tetrazine was chosen for purpose because its high reactivity and respective...
The inhibition of liver pyruvate kinase could be beneficial to halt or reverse non-alcoholic fatty disease (NAFLD), a progressive accumulation fat in the that can lead eventually cirrhosis. Recently, urolithin C has been reported as new scaffold for development allosteric inhibitors (PKL). In this work, comprehensive structure–activity analysis was carried out. More than 50 analogues were synthesized and tested regarding chemical features responsible desired activity. These data pave way...
Small-molecular fibroblast activation protein inhibitor (FAPI)-based tracer have been shown to be promising Positron Emission Tomography (PET) 68Ga-labeled radiopharmaceuticals image a variety of tumors including pancreatic, breast, and colorectal cancers, among others. In this study, we developed novel 18F-labeled FAPI derivative. [18F]6 was labeled using synthon approach based on the tetrazine ligation. It showed subnanomolar affinity for FAP good selectivity profile against known...
The potential therapeutic benefit of compounds able to activate AMPA receptors (AMPAr) has led the search for new AMPAr positive modulators. On basis crystallographic data benzothiadiazines binding mode in S1S2 GluA2 dimer interface, a set 5-aryl-2,3-dihydrobenzothiadiazine type been synthesized and tested. Electrophysiological results suggested that 5-heteroaryl substituents on benzothiadiazine core like 3-furanyl 3-thiophenyl dramatically enhance activity as modulators with respect IDRA21...