Publications

Introduction
In many situations, optimal drug therapy requires continuing, high levels of target occupancy and this notion has led pharmacologists to focus attention to the rate by which drug candidates dissociate from their target. To this end, radioligand dissociation experiments are often carried out on in vitro models such intact cells and membranes thereof but the interpretation of the collected data is sometimes ambiguous.
Areas ...

Excitatory amino acid transporters (EAATs) are important regulators of amino acid transport and in particular glutamate. Recently, more interest has arisen in these transporters in the context of neurodegenerative diseases. This calls for ways to modulate these targets to drive glutamate transport, EAAT2 and EAAT3 in particular. Several inhibitors (competitive and noncompetitive) exist to block glutamate transport; however, activators remain ...

Metastatic prostate carcinoma overexpresses prostate-specific membrane antigen (PSMA), making this antigen a suitable target for radioligand therapy of the disease. Here we report on our experience with a series of 73 castration-resistant prostate carcinoma patients treated with Ac-225-PSMA-617, identifying variables predictive for overall survival (OS) and progression-free survival (PFS) after Ac-225-PSMA-617 treatment. Methods: Ac-225-PSMA-617 ...

Drug-receptor interactions were earlier quanti?ed in terms of af?nity and ef?cacy only but residence time has now also been recognized to affect clinical performance. Different approaches to measure drug binding kinetics are brie?y presented and critically evaluated with the help of simulations. Based on the antagonist's ability to reduce agonist-evoked responses, two main methods are used in functional assays. Radiolabelled drug binding to cell ...

De cannabinoid receptor type 1 (CB1R) en cannabinoid receptor type 2 (CB 2R) zijn onderdeel van het endocannabinoid systeem, dat ook endogene lig anden zoals anandamide en 2- arachidonoyl glycerol omvat, samen met meta bolisatie- en transportproteïnen. De CB1R wordt tegenwoordig uitgebreid onderzocht omwille van zijn betrokkenheid in de therapeutische en psycho actieve effecten van cannabinoïden in het centraal zenuwstelsel. De CB2R is ...

The cannabinoid receptor type 2 (CB2R) is an attractive target for the diagnosis and therapy of neurodegenerative diseases and cancer. In this study, we aimed at the development of a novel 18F-labeled radioligand starting from the structure of the known naphthyrid-2-one CB2R ligands. Compound 28 (LU13) was identified with the highest binding affinity and selectivity versus CB1R (CB2RKi = 0.6 nM; CB1RKi/CB2RKi > 1000) and was selected for ...

Purpose As several therapies aimed at lowering mutant huntingtin (mHTT) brain levels in Huntington's disease (HD) are currently being investigated, noninvasive positron emission tomography (PET) imaging of mHTT could be utilized to directly evaluate therapeutic efficacy and monitor disease progression. Here we characterized and longitudinally assessed the novel radioligand [C-11]CHDI-626 for mHTT PET imaging in the zQ175DN mouse model of HD. ...

The development of cannabinoid receptor type 2 (CB2R) PET radioligands has been intensively explored due to the pronounced CB2R upregulation under various pathological conditions. Herein, we report on the synthesis of a series of CB2R affine fluorinated indole-2-carboxamide ligands. Compound RM365 was selected for PET radiotracer development due to its high CB2R affinity (Ki = 2.1 nM) and selectivity over CB1R (factor > 300). Preliminary in ...

PURPOSE: To evaluate the use of 68Ga-PSMA PET/CT for monitoring response to 177Lu-617 PSMA radioligand therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC). METHODS: Patients from the University Hospital Bonn and the University Hospital Aachen were retrospectively reviewed for this study. We included 48 patients with mCRPC who were treated with 177Lu-PSMA-617 and whose records included 68Ga-PSMA PET/CT imaging before ...

UNLABELLED: Phosphodiesterases are enzymes that inactivate the intracellular second messengers 3',5'-cyclic adenosine-monophosphate and/or cyclic guanosine-monophosphate. Of all 11 known phosphodiesterase families, phosphodiesterase-10A (PDE10A) has the most restricted distribution, with high expression in the striatum. PDE10A inhibitors are pursued as drugs for treatment of neuropsychiatric disorders. We have synthesized and evaluated ...