Contact

Porträt Prof. Dr. Brust, Peter; FWPN

Prof. Dr. Peter Brust
Head
p.brustAthzdr.de
Phone: +49 351 260 - 4610
Fax: +49 351 260 - 4699

Molecular imaging of α7 nAChR in cancer and brain diseases


Research

With this project we seek to develop a tool for non-invasive quantification of the α7 subtype of nicotinic acetylcholine receptors (α7 nAChR) expressed in brain to better understand the involvement of this ligand-gated Ca2+ channel in the biology of brain cancers. Based on ex vivo data, a close connection between changes in the density and functionality of α7 nAChR with various neurological disorders and most types of cancer has been assumed. But the visualization of these alterations in vivo by clinically relevant imaging technologies such as PET is still challenging due to limitations in receptor-binding radiotracers.

 

Accordingly, we are working on the design, synthesis, radiolabeling, and preclinical evaluation of 18F-labelled α7 nAChR PET radiotracers. In the past years, we have learned a great deal on the suitability of small molecules substituted with a 1,4-diazabicyclo-[3.2.2]nonane, such as [18F]DBT-10 or [18F]NS10743, for detection of α7 nAChR expressed in brain of different species.

 

[18F]DBT-10                   

Scheme of the radiosynthesis of the α7 nAChR-binding radiotracer [18F]DBT10 (Ki α7 nAChR = 0.6 nM) and uptake of [18F]DBT-10 in the brain of a rhesus monkey ( [18F]DBT-10 VT/fP and corresponding MR images).

 

Using this expertise from earlier studies in medicinal chemistry, radiochemistry, and preclinical evaluation, work aims now to characterize the expression pattern of α7 nAChR in glioblastoma.

 

To achieve this objective, we establish orthotopic tumor models in mouse and study the suitability of established and new radiotracers for the analysis of spatial and temporal changes of the expression of α7 nAChR by small animal PET/MRI studies.

Small animal PET/MR image of the tumoral [18F]NS10743 uptake in a U87-MG glioblastoma xenograft mouse.  

 

Partners

  • ABX GmbH, Radeberg, Germany
  • DanPET, Malmö, Sweden

  • Maastricht University Medical Center, Maastricht, Netherlands
  • Mahidol University, Bangkok, Thailand
  • National Cyclotron and PET Centre, Bangkok, Thailand
  • National Institute of Radiological Sciences, Inage-ku, Chiba, Japan
  • Neurosearch A/S, Hallerup, Denmark
  • Universität Leipzig, Leipzig, Germany
  • Universitätsklinikum Leipzig, Leipzig, Germany
  • Yale University, New Haven, USA

Financial support

DFG DE 1165/2-1, DFG DE 1165/2-3

Publications

  • PET imaging of α7 nicotinic acetylcholine receptors: a comparative study of [18F]ASEM and [18F]DBT-10 in nonhuman primates, and further evaluation of [18F]ASEM in humans

    Hillmer AT, Li S, Zheng MQ, Scheunemann M, Lin SF, Nabulsi N, Holden D, Pracitto R, Labaree D, Ropchan J, Teodoro R, Deuther-Conrad W, Esterlis I, Cosgrove KP, Brust P, Carson RE, Huang Y. European Journal of Nuclear Medicine and Molecular Imaging, Volume 44, Issue 6, 1 June 2017, Pages 1042-1050

  • PET imaging of α7 nicotinic acetylcholine receptors in a heterotopic xenograft model of brain cance

    Deuther-Conrad W, Neuber C, Teodoro R, Kranz M, Belter B, Peters D, Pietzsch J, Brust P. Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 60 Issue S1 Supplement: The 22nd International Symposium on Radiopharmaceutical Sciences (ISRS 2017), Dresden, Germany, May 14-19, 2017

  • PET imaging evaluation of [18F]DBT-10, a novel radioligand specific to α7 nicotinic acetylcholine receptors, in nonhuman primates

    Hillmer AT, Zheng MQ, Li S, Scheunemann M, Lin SF, Holden D, Labaree D, Ropchan J, Teodoro R, Deuther-Conrad W, Carson RE, Brust P, Huang Y. European Journal of Nuclear Medicine and Molecular Imaging, Volume 43, Issue 3, 1 March 2016, Pages 537-547

  • A promising PET tracer for imaging of α7 nicotinic acetylcholine receptors in the brain: Design, synthesis, and in vivo evaluation of a dibenzothiophene-based radioligand

    Teodoro R, Scheunemann M, Deuther-Conrad W, Wenzel B, Fasoli FM, Gotti C, Kranz M, Donat CK, Patt M, Hillmer A, Zheng MQ, Peters D, Steinbach J, Sabri O, Huang Y, Brust P. Molecules, Volume 20, Issue 10, 9 October 2015, Pages 18387-18421

  • A high-yield automated radiosynthesis of the alpha-7 nicotinic receptor radioligand [18F]NS10743

    Teodoro R, Wenzel B, Oh-Nishi A, Fischer S, Peters D, Suhara T, Deuther-Conrad W, Brust P. Applied Radiation and Isotopes, Volume 95, January 01, 2015, Pages 76-84

  • Imaging of α7 nicotinic acetylcholine receptors in brain and cerebral vasculature of juvenile pigs with [18F]NS14490

    Rötering S, Deuther-Conrad W, Cumming P, Donat CK, Scheunemann M, Fischer S, Xiong G, Steinbach J, Peters D, Sabri O, Bucerius J, Brust P. EJNMMI Research, Volume 4, Issue 1, 1 December 2014, Article number 43, Pages 1-11

  • Radiosynthesis and first evaluation in mice of [18F]NS14490 for molecular imaging of α7 nicotinic acetylcholine receptors

    Rötering S, Scheunemann M, Fischer S, Hiller A, Peters D, Deuther-Conrad W, Brust P. Bioorganic and Medicinal Chemistry, Volume 21, Issue 9, 1 May 2013, Pages 2635-2642

  • Development of radioligands for the imaging of α7 nicotinic acetylcholine receptors with positron emission tomography

    Brust P, Peters D, Deuther-Conrad W. Current Drug Targets, Volume 13, Issue 5, May 2012, Pages 594-601

  • Assessment of a7 nicotinic acetylcholine receptor availability in juvenile pig brain with [18F]NS10743

    Deuther-Conrad W, Fischer S, Hiller A, Becker G, Cumming P, Xiong G, Funke U, Sabri O, Peters D, Brust P. European Journal of Nuclear Medicine and Molecular Imaging, Volume 38, Issue 8, August 2011, Pages 1541-1549

  • Molecular imaging of α7 nicotinic acetylcholine receptors: Design and evaluation of the potent radioligand [18F]NS10743

    Deuther-Conrad W, Fischer S, Hiller A, Stergaard Nielsen E, Brunicardi Timmermann D, Steinbach J, Sabri O, Peters D, Brust P. European Journal of Nuclear Medicine and Molecular Imaging, Volume 36, Issue 5, May 2009, Pages 791-800


Contact

Prof. Dr. Peter Brust
Head
p.brustAthzdr.de
Phone: +49 351 260 - 4610
Fax: +49 351 260 - 4699