Project Details
Projekt
Development of radiolabelled butyrylcholinestase inhibitors as neurologigal biomarkers for molecular imaging by positron emission tomography
Subject Area
Pharmacy
Term
from 2012 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 214496460
The goal of this research project lies in the development of radiolabeled butyrylcholinesterase (BChE) biomarkers for positron emission tomography (PET) investigations. For this purpose a novel labelling concept will be applied for the first time, in which a radiolabeled chemical moiety is irreversibly transferred to the catalytic active center of BChE (irreversible trapping). Such carbamate-based BChE inhibitors have been developed in our group with nanomolar affinity at human BChE and excellent selectivity over the isoenzyme acetylcholinesterase (hAChE). These lead structures will be further optimized by synthetic means and in vitro evaluation supported by molecular modeling studies, in order to develop the most suitable compounds as PET radiotracers with optimal metabolic and physicochemical characteristics. Additionally, suitable synthetic pathways for preparation of 11C and 18F analogs will be developed and established with a focus on 18F labelled radiophramaceuticals. The radiolabeled highly active and selective irreversible BChE inhibitors will be evaluated as radiotracers for PET-investigations of cerebral BChE in mice applying small animal PET. Due to their innovative mode of action such compounds represent a new approach to visualize and quantify cerebral BChE as important target for diagnosis of neurodegenerative disorders.
DFG Programme
Research Grants
