Contact

Porträt Prof. Dr. Brust, Peter; FWPN

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

Development of 18F-labelled fluoroalkyl-substituted spirocyclic piperidine derivatives as PET radiotracers for the imaging of σ1 receptors in cancer and brain diseases


Unlike classical plasma-membrane bound neurotransmitter receptors the σ1 receptor resides mainly at the mitochondria-associated membranes of the endoplasmatic reticulum and interacts specifically with proteins involved in the homeostasis of the intracellular Ca2+-concentration. Currently σ1 receptor is considered as novel biological target for the pharmacological treatment of cancer and several brain diseases, e.g. depression, anxiety and neurodegeneration. This project is focused on the development of σ1 receptor imaging by PET which is useful to examine the biological function and therapeutic potential of σ1 receptor for oncology application and treatment of neurological and psychiatric disorders.

FWPN Sigma1

Radiosynthesis and ex vivo autoradiographic images of the distribution of a series of 18F-labelled fluoroalkyl-substituted spirocyclic piperidines in the brain of CD1 mice at 45 min post injection of the respective radiotracer. The localization of the radiotracers correlates with σ1 receptor-rich regions such as the area of the facial nucleus, the dorsolateral and lateral periaqueductal gray, the dorsomedial hypothalamic area, and the cerebellum. In comparison to [18F]WMS1813 and [18F]WMS1847 the fluoroethyl-substituted radiotracer [18F]Fluspidine provided superior target-to-nontarget tissue ratios and is therefore chosen for further preclinical development.

Partner

  • AG Prof. Bernhard Wünsch, Department of Pharmaceutical and Medicinal Chemistry University of Münster

  • AG Prof. Hong-Mei Jia, Department of Radioactive Pharmaceutical Chemistry, College of Chemistry, Bejing Normal University

Publications

  • Wang X, Li Y, Deuther-Conrad W, Xie F, Chen X, Cui M-C,  Zhang,X-J,  Zhang J-M, Steinbach J, Brust P, Liu B-L,  Jia H-M. Synthesis and biological evaluation of 18F labeled fluoro-oligo-ethoxylated 4-benzylpiperazine derivatives for sigma-1 receptor imaging. Bioorg. Med. Chem. 21 (2013) 215-222

  • Maisonial A, Grosse Maestrup E, Wiese C, Hiller A, Schepmann D, Deuther-Conrad W, Fischer S, Brust P, Wünsch B. Synthesis, radiofluorination and pharmacological evaluation of fluoromethyl substituted spirocyclic PET tracers for labeling of σ1 receptors in the central nervous system and comparison with longer homologues. Bioorg. Med. Chem. 20 (2012) 257-269.

  • Maisonial A, Grosse Maestrup E, Fischer S, Hiller A, Scheunemann M, Wiese C, Schepmann D, Steinbach J, Deuther-Conrad W, Wünsch B, Brust P. A 18F-labeled fluorobutyl-substituted spirocyclic piperidine derivative as a selective radioligand for PET Imaging of sigma1 receptors. ChemMedChem. 2011,6(8):1401-10.

  • Fischer S, Wiese C, Maestrup EG, Hiller A, Deuther-Conrad W, Scheunemann M, Schepmann D, Steinbach J, Wünsch B, Brust P.Molecular imaging of σ receptors: synthesis and evaluation of the potent σ1 selective radioligand [18F]fluspidine.Eur J Nucl Med Mol Imaging. 2011,38(3):540-51.

  • Maestrup EG, Fischer S, Wiese C, Schepmann D, Hiller A, Deuther-Conrad W, Steinbach J, Wünsch B, Brust P. Evaluation of spirocyclic 3-(3-fluoropropyl)-2-benzofurans as sigma1 receptor ligands for neuroimaging with positron emission tomography. J Med Chem. 2009,52(19):6062-72.

  • Grosse Maestrup E, Wiese C, Schepmann D, Hiller A, Fischer S, Scheunemann M, Brust P, Wünsch B. Synthesis of spirocyclic sigma1 receptor ligands as potential PET radiotracers, structure-affinity relationships and in vitro metabolic stability. Bioorg Med Chem. 2009,17(10):3630-41.


Contact

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