Toxic epibatidine was structurally modified to image Alzheimer´s disease

Brust Group | Helmholtz-Zentrum Dresden-Rossendorf, Germany

cat icon February 21 2014 | 10:07 min
Category: Lab

Related article:

Löser, R.; Fischer, S.; Hiller, A.; Köckerlin, M.; Funke, U.; Maisonial, .A.; Brust, P.; Steinbach, J., Beilstein J. Org. Chem. 2013, 9, 1002-1011. 10.3762/bjoc.9.115



The video describes the process of the development of a radiopharmaceutical for imaging of Alzheimer´s disease with positron emission tomography. The toxin epibatidine, which was originally derived from a poison arrow frog, is known to bind to various subtypes of nicotinic acetylcholine receptors. Those with an alpha1 subunit are mainly responsible for the toxic action, those with alpha4 and alpha7 subunits are important for Alzheimer´s disease. Structural modification allowed avoidance of the toxic action. The new molecule, called flubatine, contains fluorine in 6-position of a pyridine which was exchanged by the cyclotron-produced positron emitter fluorine-18. Successful in vitro and preclinical in vivo
characterization of the radiolabelled flubatine allowed radiopharmaceutical production and use of the compound for PET imaging of patients with Alzheimer´s disease.

Peter Brust is head of the Neuroradiopharmaceuticals Division at the Helmholtz-Zentrum Dresden-Rossendorf, Research Site Leipzig, and professor at the Faculty of Biosciences, Pharmacy and Psychology of Universität Leipzig. He is neuroscientist and expert in the fields of animal physiology, blood-brain barrier, radiopharmacology and neuroimaging.

Matthias Scheunemann is organic chemist and senior scientist in the group.

Karsten Franke is physicist, cyclotron operator and senior scientist in the group.

Barbara Wenzel is chemist, specialized in radiochemistry and senior scientist in the group.

Winnie Deuther-Conrad is biochemist, specialized in radiopharmacology and senior scientist in the group.

Mathias Kranz is health physicist, specialized in radiation dosimetry and PhD student in the group.

Brust, P.; Patt, J.T.; Deuther-Conrad, W.; Becker, G.; Patt, M.; Schildan, A.; Sorger, D.; Kendziorra, K.; Meyer, P.; Steinbach, J.; Sabri, O., In vivo measurement of nicotinic acetylcholine receptors with [18F]norchloro-fluoro-homoepibatidine, Synapse 2008, 3, 205-218. 10.1002/syn.20480

Smits, R.; Fischer, S.; Hiller, A.; Deuther-Conrad, W.; Wenzel, B.; Patt, M.; Cumming, P.; Steinbach, J.; Sabri, O.; Brust, P.; Hoepping, A., Synthesis and biological evaluation of both enantiomers of [18F]flubatine, promising radiotracers with fast kinetics for the imaging of α4β2-nicotinic acetylcholine receptors, J. BMC 2014, 2, 804-812. 10.1016/j.bmc.2013.12.011

Patt, M.; Schildan, A.; Habermann, B.; Fischer, S.; Hiller, A.; Deuther-Conrad, W.; Wilke, S.; Smits, R.; Hoepping, A.; Wagenknecht, G.; Steinbach, J.; Brust, P.; Sabri, O., Fully automated radiosynthesis of both enantiomers of [18F]Flubatine under GMP conditions for human application, Applied Radiation and Isotopes 2013, 80, 7-11. 10.1016/j.apradiso.2013.05.009

Fischer, S.; Hiller, A.; Smits, R.; Hoepping, A.; Funke, U.; Wenzel, B.; Cumming, P.; Sabri, O.; Steinbach, J.; Brust, P., Radiosynthesis of racemic and enantiomerically pure (−)-[18F]flubatine—A promising PET radiotracer for neuroimaging ofα4β2 nicotinic acetylcholine receptors, Applied Radiation and Isotopes 2013, 74, 128-136. 10.1016/j.apradiso.2013.01.002