Porträt Prof. Dr. Brust, Peter; FWPN

Prof. Dr. Peter Brust
Phone: +49 351 260 - 4610
Fax: +49 351 260 - 4699

Development of new ligands and 18F-radiotracers for the vesicular acetylcholine transporter (VAChT) in brain

Aim of this project is the development of PET-radiotracers for imaging of cholinergic alterations in brain. As component of cholinergic presynapse, the VAChT is studied as potential target structure to visualize and quantify terminal deficits in the cholinergic system in brain.

Since 2000 our group is engaged in the design, synthesis, radiosynthesis, and biological evaluation of new 18F-labeled VAChT-radioligands. All ligands developed so far are based on the lead structure vesamicol, the only compound known to bind with high affinity to the transporter. With the design of structurally modified vesamicol analogs especially the selectivity has to be considered, because of possible binding to sigma receptors, which are also present in many brain regions.

FWPN VAChT - slice

FWPN VAChT - illustration

FWPN VAChT - compounds

Ex vivo autoradiogram of coronal rat brain slice, 60 min after injection of [18F]FBMV

modified from Löffler, Petrides, Heinrich (Ed.),  Biochemie und Pathologie, 2007

Vesamicol and selected VAChT ligands developed in the Department of Neuroradiopharmaka


  • Department of Nuclear Medicine, University of Leipzig
  • AG Prof. G. Schüürmann, Department Ecological Chemistry, Helmholtz Centre for Environmental Research (UFZ), Leipzig

  • Birla Institute of Technology & Science Pilani, Hyderabad, India

  • Uppsala University, Uppsala, Sweden


  • M. Lindemann, W. Deuther-Conrad, R. Moldovan, KVG. Chandra Sekhar, P. Brust, B. Wenzel; "Do spiroindolines have the potential to replace vesamicol as lead compound for the development of radioligands targeting the vesicular acetylcholine transporter?" Bioorg. Med. Chem. 2017, doi: 10.1016/j.bmc.2017.03.028.
  • S. Roslin, M. De Rosa, W. Deuther-Conrad, LR. Odell, G. Antoni, P. Brust, M. Larhed; "Synthesis and in vitro evaluation of 5-substituted benzovesamicol analogs containing N-substituted amides as potential positron emission tomography tracers for the vesicular acetylcholine transporter"; Bioorg. Med. Chem. 2017, doi: 10.1016/j.bmc.2017.01.041.
  • C. Barthel, D. Sorger, W. Deuther-Conrad, M. Scheunemann, S. Schweiger, P. Jäckel, A. Roghani, J. Steinbach, G. Schüürmann, O. Sabri, P. Brust, B. Wenzel; "New systematically modified vesamicol analogs and their affinity and selectivity versus the VAChT – A critical examination of the lead structure"; Eur. J. Med. Chem. 2015, 100, 50-67.
  • B. Wenzel, Y. Li, W. Kraus, D. Sorger, O. Sabri, P. Brust, O. Sabri, J. Steinbach; "Pyrrolovesamicols-Synthesis, structure and VAChT binding of two 4-fluorobenzoyl regioisomers"; Bioorg. Med. Chem. Lett. 22 (2012) 2163-2166.

  • B. Wenzel, A. Hiller, S. Fischer, D. Sorger, W. Deuther-Conrad, M. Scheunemann, P. Brust, O. Sabri, J. Steinbach; "In vitro binding profile and radiosynthesis of a novel 18F-labeled azaspirovesamicol analog as potential ligand for imaging of the vesicular acetylcholine transporter“; J. Lab. Comp. Radiopharm. 54 (2011) 426-432.

  • B. Wenzel, S. Fischer, P. Brust, J. Steinbach; "Accessible silanol sites - Beneficial for the RP-HPLC separation of constitutional and diastereomeric azaspirovesamicol isomers“; J. Chromatogr. A 1217 (2010) 7884-7890.

  • B. Wenzel, S. Fischer, P. Brust, J. Steinbach; "Enantioseparation of vesamicol and novel vesamicol analogs by high-performance liquid chromatography on different chiral stationary phases“; J. Chromatogr. A 1217 (2010) 3855-3862.

  • D. Sorger, M. Scheunemann, J. Vercouillie, U. Großmann, S. Fischer, A. Hiller, B. Wenzel, A. Rhogani, R. Schliebs, J. Steinbach P. Brust, O. Sabri,; "Neuroimaging of the vesicular acetylcholine transporter by a novel 4-[18F]fluoro-benzoyl derivative of 7-hydroxy-6-(4-phenyl-piperidin-1-yl)octahydro-benzo[1,4]oxazines“; Nucl. Med. Biol. 36 (2009) 17-27.

  • Szymoszek, B. Wenzel, M. Scheunemann, J. Steinbach, G. Schüürmann; "First CoMFA Characterization of Vesamicol Analogs as Ligands for the Vesicular Acetylcholine Transporter“; J. Med. Chem. 51 (2008) 2128-2136.

  • D. Sorger, M. Scheunemann, U. Großmann, S. Fischer, J. Vercouille, A. Hiller, B. Wenzel, A. Rhogani, R. Schliebs, P. Brust, O. Sabri, J. Steinbach; "A new 18F-labeled fluoroacetylmorpholino derivative of vesamicol for neuroimaging of the vesicular acteylcholine transporter“; Nucl. Med. Biol. 35 (2008) 185-195.

  • B. Wenzel, J. W. Bats, M. Scheunemann, J. Steinbach; "Azaspirovesamicols - Regioselective synthesis and crystal structure analysis of a novel class of vesamicol analogues as potential ligands for the vesicular acetylcholine transporter"; Chem. Lett. 36 (2007) 276-277.

  • M. Scheunemann, D. Sorger, E. Kouznetsova, O. Sabri, R. Schliebs, B. Wenzel, J. Steinbach; "Sequential ring-opening of trans-1,4-cyclohexadiene dioxide for an expedient modular approach to 6,7-disubstituted (±)-hexahydro-benzo[1,4]oxazin-3-ones“; Tetrahedron Lett. 48 (2007) 5497-5501.

  • B. Wenzel, D. Sorger, K. Heinitz, M. Scheunemann, R. Schliebs, J. Steinbach, O. Sabri; "Structural changes of benzylether derivatives of vesamicol and their influence on the binding selectivity to the vesicular acetylcholine transporter"; Eur. J. Med. Chem. 40 (2005) 1197-1205.

  • M. Scheunemann, D. Sorger, B. Wenzel, K. Heinitz, R. Schliebs, M. Klingner, O. Sabri, J. Steinbach; "Synthesis of novel benzyl ether derivatives of vesamicol and in vitro evaluation of their binding properties to the vesicular acetylcholine transporter site"; Bioorg. Med. Chem., 12 (2004) 1459-1465.

Financial Support by

  • Deutsche Forschungsgemeinschaft – DFG (WE 2927/1-1, WE 2927/1-2, and WE 2927/4-1)

  • Sächsisches Ministerium für Wissenschaft und Kunst - SMWK


Prof. Dr. Peter Brust
Phone: +49 351 260 - 4610
Fax: +49 351 260 - 4699