Matthias M Herth

University of Copenhagen · Department of Drug Design and Pharmacology

The glymphatic system is a brain-wide waste drainage system that promotes cerebrospinal fluid circulation through the brain to remove waste metabolites. Currently, the most common methods for assessing glymphatic function are ex vivo fluorescence microscopy of brain slices, macroscopic cortical imaging, and MRI. While all these methods have been cr...

Repeated low doses of psilocybin reduce compulsive actions and increase synaptic connections in the paraventricular thalamic nucleus of the rat

RationaleThe psychedelic effects of the traditional Amazonian botanical decoction known as ayahuasca are attributed to the effects of N,N-dimethyltryptamine (DMT) at brain serotonin 5-HT2A receptors. To make oral DMT bioavailable, ayahuasca additionally contains reversible monoamine oxidase A (MAO-A) inhibitors, namely β-carboline alkaloids such as...

The SARS-CoV2 Omicron variant sub-lineages spread rapidly through the world, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for anti-SARS-CoV-2 agents that are effective against emergent strains in vulnerable patients. Camelid nanobodies are attrac...

Human serum albumin (HSA) has been shown to be a promising tumor targeting vector and target for generating theranostics by bioconjugation. Unstable chemical conjugation to HSA via a cysteine (Cys34) by reversible Michael additions is most commonly applied for this purpose. Herein, we describe utilization of our recently developed site-selective ir...

Pretargeting imaging has gained a lot of prominence, due to its excellent bioorthogonality and improved imaging contrast compared to conventional imaging. A new iodo tetrazine (Tz) derivative has been synthesized and further developed into the corresponding iodine‐125 (125I) analogue (12), via the trimethylstannane precursor. Radiolabeling with eit...

Tetrazine (Tz)-trans-cyclooctene (TCO) ligation is an ultra-fast and highly selective reaction and it is particularly suited to label biomolecules under physiological conditions. As such, a 3 H-Tz based synthon would have wide applications for in vitro/ex vivo assays. In this study, we developed a 3 H-labeled Tz and characterized its potential for...

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 are a histopathological hallmark. The radiotracer (d3)-[¹¹C]MODAG-001 has recently shown promise for visu...

COVID-19, caused by the SARS-CoV-2 virus, has become a global pandemic that is still present after more than two years. COVID-19 is mainly known as a respiratory disease that can cause long-term consequences referred to as long COVID. Molecular imaging of SARS-CoV-2 in COVID-19 patients would be a powerful tool for studying the pathological mechani...

Tucatinib is a selective human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitor approved by the U.S. Food and Drug Administration (FDA) in April 2020 for HER2-positive lesions in metastatic breast cancer patients, including CNS metastases. In this article, we attempted to develop the first small molecule, blood-brain-barrier (BBB...

Pretargeting is a promising nuclear imaging technique that allows for the usage of antibodies (Abs) with enhanced imaging contrast and reduced patient radiation burden. It is based on bioorthogonal chemistry with the tetrazine ligation—a reaction between trans-cyclooctenes (TCOs) and tetrazines (Tzs)—currently being the most popular reaction due to...

The blood-brain barrier (BBB) is a protective and semipermeable border of endothelial cells that prevents toxins and foreign bodies to enter and damage the brain. Unfortunately, the BBB also hampers the development of pharmaceuticals targeting receptors, enzymes, or other proteins that lie beyond this barrier. Especially large molecules, such as mo...

Alzheimer's disease (AD) is the most common neurodegenerative disease, with an increasing prevalence. Currently, there is no ideal diagnostic molecular imaging agent for diagnosing AD. Antibodies (Abs) have been proposed to close this gap as they can bind selectively and with high affinity to amyloid β (Aβ)—one of the molecular hallmarks of AD. Abs...

Background The development of radiopharmaceuticals requires extensive evaluation before they can be applied in a diagnostic or therapeutic setting in Nuclear Medicine. Chemical, radiochemical, and pharmaceutical parameters must be established and verified to ensure the quality of these novel products. Main body To provide supportive evidence for t...

Astatine-211 (211At) is one of the most promising α-emitters for targeted alpha therapy, especially of cancer metastases. However, the lack of a stable isotope, frequent in vivo deastatination, and limited radiochemical knowledge makes it challenging to apply. Here, we report a new strategy for radiolabeling the lipophilic core of polymeric micelle...

Combining nanotechnology and bioorthogonal chemistry for theranostic strategies offers the possibility to develop next generation nanomedicines. These materials are thought to increase therapeutic outcome and improve current cancer management. Due to their size, nanomedicines target tumors passively. Thus, they can be used for drug delivery purpose...

Radiolabeling of tetrazines has gained increasing attention due to their important role in pretargeted imaging or therapy. The most commonly used radionuclide in PET imaging is fluorine-18. For this reason, we have recently developed a method which enables the direct aromatic 18F-fluorination of tetrazines using stannane precursors through copper-m...

Tetrazine ligation has gained interest as a bio-orthogonal chemistry tool within the last decade. In nuclear medicine, tetrazine ligation is currently being explored for pretargeted approaches, which have the potential to revolutionize state-of-the-art theranostic strategies. Pretargeting has been shown to increase target-to-background ratios for r...

Pretargeting is a powerful nuclear imaging strategy to achieve enhanced imaging contrast for nanomedicines. It reduces the radiation burden to healthy tissue. Pretargeting is based on bioorthogonal chemistry. The most attractive reaction for this purpose is currently the tetrazine ligation, which occurs between trans-cyclooctene (TCO) tags and tetr...

Pretargeting is a powerful nuclear imaging strategy to achieve enhanced imaging contrast for nanomedicines. It reduces the radiation burden to healthy tissue. Pretargeting is based on bioorthogonal chemistry. The most attractive reaction for this purpose is currently the tetrazine ligation, which occurs between trans-cyclooctene (TCO) tags and tetr...

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 the radiation burden. We have recently reported a strategy to directly 18 F-label highly reactive tetrazin...

Pretargeted PET imaging is an emerging and fast-developing method to monitor immuno-oncology strategies. Currently, tetrazine ligation is considered the most promising bioorthogonal reaction for pretargeting in vivo. Recently, we have developed a method to 18F-label ultrareactive tetrazines by copper-mediated fluorinations. However, bispyridyl tetr...

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 a histopathological hallmark. The radiotracer (d 3 )-[ ¹¹ C]MODAG-001 has recently shown promise for v...

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 a histopathological hallmark. The radiotracer (d3)-[¹¹C]MODAG-001 has recently shown promise for visu...

Pretargeting is a powerful nuclear imaging strategy to achieve enhanced imaging contrast for nanomedicines and reduce the radiation burden to healthy tissue. Pretargeting is based on bioorthogonal chemistry. The most...

Fluorine-18 displays almost ideal decay properties for positron emission tomography (PET) and allows for large scale production. As such, simplified methods to radiolabel peptides with fluorine-18 are highly warranted. Chelation of aluminium fluoride-18 toward specific peptides represents one method to achieve this. With the current methods, chelat...

Functionalization of macromolecules (antibodies, polymers, nanoparticles) with click-reactive groups greatly enhances the versatility of their potential applications. Click chemistry based on tetrazine – trans-cyclooctene (TCO) ligation is especially promising and is already widely applied for pretargeted imaging and therapy. Indirect radiolabeling...

Introduction Radiotherapy of cancer requires both alpha and beta-particle emitting radionuclides, as these radionuclide types are efficient at destroying different types of tumors. Both classes of radionuclides require a vehicle, such as an antibody or a polymer, to be delivered and retained within the tumor. Polyglutamic acid (pGlu) is a polymer t...

Parkinson’s disease (PD) is caused by progressive neurodegeneration and characterised by motor dysfunction. Neurodegeneration of dopaminergic neurons also causes aberrations within the cortico-striato-thalamo-cortical (CSTC) circuit, which has been hypothesised to lead to non-motor symptoms such as depression. Individuals with PD have both lower sy...

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 the radiation burden. We have recently reported a strategy to directly 18F-label highly reactive tetrazines...

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 the radiation burden. We have recently reported a strategy to directly 18F-label highly reactive tetrazines...

Targeted α-therapy (TAT) can eradicate tumor metastases while limiting overall toxicity. One of the most promising α-particle emitters is astatine-211 (211At). However, 211At-carbon bonds are notoriously unstable in vivo and no chelators are available. This hampers its adoption in TAT. In this study, the stability of 211At on the surface of gold na...

Parkinson’s disease (PD) is a neurodegenerative disorder that affects millions of people worldwide. Two hallmarks of PD are the accumulation of alpha-synuclein and the loss of dopaminergic neurons in the brain. There is no cure for PD, and all existing treatments focus on alleviating the symptoms. PD diagnosis is also based on the symptoms, such as...

Neurodegenerative diseases such as Parkinson’s disease (PD) are manifested by inclusion bodies of alpha-synuclein (α-syn) also called α-synucleinopathies. Detection of these inclusions is thus far only possible by histological examination of postmortem brain tissue. The possibility of non-invasively detecting α-syn will therefore provide valuable i...

Aliphatic nucleophilic substitution (S N 2) with [ 18 F]fluoride is the most widely applied method to prepare 18 F-labeled positron emission tomography (PET) tracers. Strong basic conditions commonly used during 18 F-labeling procedures inherently limit or prohibit labeling of base-sensitive scaffolds. The high basicity stems from the tradition to...

Pretargeted imaging can be used to visualize and quantify slow-accumulating targeting vectors with short-lived radionuclides such as fluorine-18 - the most popular clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-live...

Pretargeted imaging can be used to visualize and quantify slow-accumulating targeting vectors with short-lived radionuclides such as fluorine-18 – the most popular clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using long-live...

In the struggle to understand and accurately diagnose Parkinson′s disease, radiopharmaceuticals and medical imaging techniques have played a major role. By being able to image and quantify the dopamine transporter density, noninvasive diagnostic imaging has become the gold standard. In the shift from the first generation of SPECT tracers, the fluor...

Aliphatic fluorine‐18 radiolabeling is the most commonly used method to synthesize tracers for PET‐imaging. With an increasing demand for 18 F‐radiotracers for clinical applications, new labeling strategies aiming to increase radiochemical yields of established tracers or more importantly to enable 18 F‐labeling of new scaffolds have been developed...

p>Pretargeting imaging of nanomedicines have attracted considerable interest in nuclear medicine since it has the potential to increase imaging contrast while simultaneously reducing radiation burden to healthy tissue. Currently, the tetrazine ligation is the fastest bioorthogonal reaction available for this strategy and consequently, the state-of-...

Aliphatic nucleophilic substitution (S_N2) with [¹⁸F]fluoride is the most widely applied method to prepare ¹⁸F-labeled positron emission tomography (PET) tracers. Strongly basic conditions commonly used during ¹⁸F-labeling procedures inherently limit or prohibit labeling of base-sensitive scaffolds. The hi...

Purpose: The study demonstrates the use of Desorption Electrospray Ionization mass spectrometry imaging (DESI-MSI) for imaging of the PET tracer compound Cimbi-36 in brain tissue and compares imaging by DESI-MSI to imaging by autoradiography and PET. Procedures: Rats were dosed intraperitoneally with 3 mg/kg of Cimbi-36 and euthanized at t = 5,...

Pretargeted bioorthogonal imaging can be used to visualize and quantify slow accumulating targeting vectors with short-lived radionuclides such as fluorine-18 - the most clinically applied Positron Emission Tomography (PET) radionuclide. Pretargeting results in higher target-to-background ratios compared to conventional imaging approaches using lon...

The development of highly selective and fast biocompatible reactions for ligation and cleavage has paved the way for new diagnostic and therapeutic applications of pretargeted in vivo chemistry. The concept of bioorthogonal pretargeting has attracted considerable interest, in particular for the targeted delivery of radionuclides and drugs. In nucle...

Radiochemical conversion is an important term to be included in the “Consensus nomenclature rules for radiopharmaceutical chemistry”. Radiochemical conversion should be used to define reaction efficiency by measuring the transformation of components in a crude reaction mixture at a given time, whereas radiochemical yield is better suited to define...

Personalized medicine is becoming an integral part of our healthcare system, in which theranostics play a fundamental role. Nanomedicines such as monoclonal antibodies are a commonly used targeting vector in such approaches due to their outstanding targeting abilities as well as their capabilities to function as drug delivery vehicles. However, the...

Pretargeted nuclear imaging for the diagnosis of various cancers is an emerging and fast developing field. The tetrazine ligation is currently considered the most promising reaction in this respect. Monoclonal antibodies are often the preferred choice as pretargeting vector due to their outstanding targeting properties. In this work, we evaluated t...

p>The development of highly selective and fast biocompatible reactions for ligation and cleavage has paved the way for new diagnostic and therapeutic applications of in vivo chemistry. The concept of bioorthogonal pretargeting has attracted considerable interest, in particular for the targeted delivery of radionuclides and drugs. In nuclear medicin...