Prof. Dr. Peter Brust - Department of Neuroradiopharmaceuticals

Bild Prof. Dr. Brust

Research Interest  -   Projects  -   Selected Publications  -   Work Experience   -   Memberships


Current Research Interests

Radiotracer Development for Brain Imaging with Positron Emission Tomography (PET)

  • Neuroimaging of the cholinergic system (nicotinic acetylcholine receptors, vesicular acetylcholine transporter)
  • Neuroimaging of second messenger systems (phosphodiesterase 10)
  • Neuroimaging of neuromodulatory processes (sigma and cannabinoid receptors)
  • Blood-brain barrier transport of radiopharmaceuticals

Projects

Ongoing Projects

Completed projects

  • Neuroimaging of experimental brain trauma: Characterization of potential targets for radiotracer development within the cholinergic and cannabinoid receptor system of the brain. In cooperation with Department of Neurosurgery and Paul Flechsig Institute of Brain Research, University of Leipzig and Institute of Molecular Cell Biology, Friedrich Schiller University Jena.
  • PET imaging of GABAergic neurotransmission: Development and biological characterization of new subtype specific 18F-labelled radiotracers for imaging the GABAA receptor. In cooperation with Department of Neurology, University of Leipzig and ABX GmbH Radeberg.
  • PET tracers for imaging the serotonin transporter, Part 2 Indolylcyclohexylamines Development and biological characterization of new 18F-labelled radiotracers for serotonin transporter imaging. In cooperation with Department of Nuclear Medicine, University of Leipzig and the Hebrew University Jerusalem, Israel.
  • PET tracers for imaging the serotonin transporter, Part 1 McN5652 derivatives The 18F-labelled derivative of McN5652 is superior to [11C]McN5652 for serotonin transporter imaging in preclinical studies.
  • PET tracers for tumor imaging, Part 2 thymidine kinase: Evidence that radiolabelled FIAU should be preferred as reporter probe for PET imaging of HSV1-tk gene expression compared to FHPG. Research Center Dresden-Rossendorf in cooperation with Department of Nuclear Medicine, Technische Universität München.
  • PET tracers for tumor imaging, Part 1 estrone sulfatase: The estrone sulfatase inhibitor FESDS was found to bind with high affinity also to carbonic anhydrase precluding the use of this compound for tumor imaging.  Research Center Dresden-Rossendorf in cooperation with the Hans Knöll Institute Jena.
  • PET studies of dopamine synthesis and metabolism during hypoxia: The activity of the enzyme aromatic amio acid decarboxylase is increased, the monoamine oxidase acitivity is decreased in newborn piglets during hypoxia. Research Center Dresden-Rossendorf in cooperation with the , Friedrich Schiller University Jena.
  • 99mTc-labelled receptor and transporter ligands: Characterization of serotonin receptor, dopamine receptor and dopamine transporter binding of 99m. Research Center Dresden-Rossendorf.
  • In vitro model of the blood-brain barrier: Expression of serotonin transporter, P-glycoprotein, and carnitine transporter at immortalized rat brain endothelial cells. Research Center Dresden-Rossendorf in cooperation with Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta USA.
  • PET studies of blood-brain barrier transport: Vasopressin alters the blood-brain barrier transport of methionine in dogs. Institute of Biology, University of Leipzig in cooperation with the Montreal Neurological Institute and Johns Hopkins University Baltimore.
  • Effects of nootropics on the blood-brain barrier: Reversal of ethanol-induced effects on blood-brain barrier permeability by nootropics. Institute of Biology, University of Leipzig in cooperation with drug industry (Arzneimittelwerk Dresden).
  • Intestinal amino acid transport: Beta-casomorphin increases the intestinal transport of amino acids in rats. Institute of Biology, University of Leipzig in cooperation with Department of Biochemistry, Martin-Luther-University Halle-Wittenberg.
  • Water permeability of the blood-brain barrier: Atriopeptin increases the water permeability of the blood-brain barrier in rats. Institute of Biology University of Leipzig in cooperation with Institute for Surgical Research, Ludwig-Maximilians-University, Munich.
  • Blood-brain barrier permeability for amino acids: The neuropeptide vasopressin modulates the transport of large neutral amino acids across the blood-brain barrier in rats. PhD Theses at the Institute of Biology, University of Leipzig, in cooperation with Academy of Sciences of the Czech Republik, Prague.
  • Immune tolerance: Induction of immune tolerance against human lymphocytes in mice. Diploma Thesis at the Institute of Biology of Leipzig

Selected Publications

  • Brust P., Peters D., Deuther-Conrad W. (2012) Development of radioligands for α7-nAChR imaging with positron emission tomography. Curr Drug Targets 13, 594-601.
  • Rühl T.,Deuther-Conrad W., Fischer S., Günther R., Hennig L., Krautscheid H., Brust P. (2012) Cannabinoid receptor type 2 (CB2) selective N-arylamide oxadiazoles: synthesis, biological evaluation and molecular modeling. Org. Med. Chem. Lett 2: 32,
  • Maisonial A., Grosse Maestrup E., Wiese C., Hiller A., Schepmann D., Deuther-Conrad W., Fischer S., Brust P., and Wünsch B., (2012) Synthesis, radiofluorination and pharmacological evaluation of a fluoromethyl spirocyclic PET tracer for central σ1 receptors and comparison with fluoralkyl homologues. Bioorg. Med. Chem.  20, 257–269.
  • Hesse S., Brust P., Mäding P., Becker G.-A., Seese A., Patt M., Sorger D., Zessin J., Sacher J., Lobsien D., Habermann B., Meyer PM., Füchtner F., Luthardt J., Bresch A., Steinbach J., Sabri O. (2012) Imaging of the brain serotonin transporters (SERT) with the new fluorine-18 labelled fluoromethyl-McN5652 and PET in humans. Eur. J. Nucl. Med. 39, 1001-1011.
  • Fischer S., Wiese C., Grosse Maestrup E., Hiller A., Deuther-Conrad W., Scheunemann M., Schepmann D., Steinbach J., Wünsch B., Brust P. (2011) Molecular imaging of sigma receptors: synthesis and evaluation of the potent sigma1 selective radioligand [18F]fluspidine. Eur. J. Nucl. Med. Mol. Imaging 38, 540-551.
  • Hesse S., Stengler K., Regenthal R., Patt M., Becker G.-A., Franke A., Knüpfer H., Meyer P.M., Luthardt J. , Jahn I., Lobsien D., Heinke W., Brust P., Hegerl U., Sabri O. (2011) The serotonin transporter availability in untreated early and late onset patients with obsessive-compulsive disorder. Int. J. Neuropsychopharmacol. 14, 6606-617.
  • Grosse Maestrup E., Wiese C., Schepmann D., Brust P., Wünsch B. (2011) Synthesis, pharmacological activity and structure-affinity relationships of spirocyclic sigma1 receptor ligands with a (2-fluoroethyl) residue in 3-position. Bioorg. Med. Chem. 19, 393-405.
  • Wiese C., Grosse Maestrup E., Schepmann D., Grimme S., Humpf H., Brust P., Wünsch B. (2011) Enantioselective sigma1 receptor binding and biotransformation of the spirocyclic PET tracer [1’-benzyl-3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4’-piperidine]. Chirality 23, 148-154.
  • Hoffmeister P.-G., Donat C.K., Schuhmann M.S., Voigt C., Walter B., Nieber K., Meixensberger J., Bauer R., Brust P. (2011) Alterations of alpha7 nicotinic receptors after traumatic brain injury are similar in newborn and adult animals. Neuromol. Med. 13, 44-53.
  • Wenzel, B., Fischer, S., Brust P., and Steinbach J. (2010) Accessible silanol sites - beneficial for the RP-HPLC separation of constitutional and diastereomeric azaspirovesamicol isomers. J. Chromatography A 1217, 7884-7890.
  • Donat C.K., Walter B., Deuther-Conrad W., Nieber K., Bauer R., Brust P. (2010) Alterations of cholinergic receptors and the vesicular acetylcholine transporter after lateral fluid percussion injury in newborn piglets. Neuropathol. Appl. Neurobiol. 36,225-236.
  • Wenzel, B., Fischer, S., Brust P., and Steinbach J. (2010) Enantioseparation of vesamicol and novel vesamicol analogs by high-performance liquid chromatography on different chiral stationary phases. J. Chromatography A 1217, 3855-3862.
  • Donat C.K., Walter B., Kayser T., Deuther-Conrad W., Schliebs R., Nieber K., Bauer R., Härtig W., Brust P. (2010) Effects of lateral fluid percussion injury on cholinergic markers in the newborn piglet. Int. J. Dev, Neurosci. 28, 31-38.
  • Meyer P, Strecker K, Kendziorra K, Becker G, Hesse S, Woelpl D, Hensel A, Patt M, Sorger D, Wegner F, Lobsien D, Barthel H, Brust P., Gertz HJ, Sabri O, Schwarz J, (2009) Reduced alpha4beta2* nicotinic acetylcholine receptor binding and its relationship to cognitive and depressive symptoms in Parkinson’s disease. Arch. Gen. Psychiat. 66, 866-877.
  • Große Maestrup, E., Fischer, S., Wiese, C., Schepmann, D., Hiller, A., Deuther-Conrad, W., Steinbach, J., Wünsch, B., Brust P. (2009) Evaluation of spirocyclic 3-(3-fluoropropyl)-2-benzofurans as sigma1 receptor ligands for neuroimaging with positron emission tomography. J. Med. Chem. 52, 6062-6072.
  • Deuther-Conrad, W., Fischer, S., Hiller, A., Østergaard Nielsen, E., Brunicardi Timmermann, D., Steinbach, J., Sabri, O., Peters, D., Brust P. (2009) Molecular imaging of α7 nAChR: design and evaluation of the potent radioligand [18F]NS10743. Eur. J. Nucl. Med. 93, 791-800.
  • Donat C.K., Schuhmann M.U., Voigt C., Nieber K., Deuther-Conrad W., Brust P. (2008) Time-dependent alterations of cholinergic markers after experimental traumatic brain injury. Brain Res. 1246, 167-177.
  • Ben Daniel R.; Deuther-Conrad W., Scheunemann M., Steinbach J., Brust P., Mishani E. (2008) Carbon-11 labeled indolylcyclohexylamine analogues as new potential PET agents for imaging of the serotonin transporter. Bioorg. Med. Chem. 16, 6364-6370 .
  • Brust P., Patt J.T., Deuther-Conrad W., Becker G., Patt M., Schildan A., Sorger D., Kendziorra K., Meyer P., Steinbach J., Sabri O. (2008) In vivo measurement of nicotinic acetylcholine receptors with [18F]norchloro-fluoro-homoepibatidine (NCFHEB). Synapse 62, 205-218 .
  • Hoepping A., Scheunemann M., Fischer S., Deuther-Conrad W., Hiller A., Wegner F., Diekers M., Steinbach J., Brust P. (2007) Radiosynthesis and biological evaluation of a 18F-labelled derivative of the novel pyrazolopyrimidine sedative-hypnotic agent indiplon. Nucl Med. Biol. 34, 559-570 .
  • Makrides V., R. Bauer, W. Weber, H.-J. Wester, S. Fischer, R. Hinz, K. Huggel, T. Opfermann, M. Herzau, V. Ganapathy, F. Verrey, P. Brust (2007) Preferred transport of O-(2-[18F]fluoroethyl)-D-tyrosine (D-FET) compared to [18F]L-FET and 3-O-methyl-6-[18F]fluoro-L-DOPA. Brain Res 1147, 25-33.
  • Brust P., Hesse S., Müller U., Szabo Z. (2006) Neuroimaging of the serotonin transporter - possibilities and pitfalls. Curr. Psychiat. Rev., 2, 111-149
  • Deuther-Conrad W., Wevers A., Schildan A., Becker G., Patt M., Sabri. O., Steinbach J., Brust P. (2006) Autoradiography of nicotinic acetylcholine receptors in the porcine brain in vitro. Synapse, 59, 201-210.
  • Bauer R., Walter B., Vorwieger G., Fritz A., Füchtner F., Zwiener U., Brust P. (2005) Effect of moderate hypercapnic hypoxia on cerebral dopaminergic activity and brain O2 uptake in intrauterine growth restricted newborn piglets. Pediat. Res., 57, 363-370.
  • Walter B., Brust P., Füchtner F., Müller M., Hinz R., Kuwabara H., Fritz H., Zwiener U., Bauer R. (2004) Age-dependent effects of severe traumatic brain injury on cerebral dopaminergic activity in newborn and juvenile pigs. J. Neurotrauma, 21, 1076-1089.
  • Kretzschmar M., Brust P., Zessin J., Cumming P., Bergmann R., Johannsen B. (2003) Autoradiographic imaging of the serotonin transporter in the brain of rats and pigs using S-([18F]Fluoromethyl)-(+)-McN5652. Eur. Neuropsychopharmacol. 13, 387-397.
  • Brust P., Hinz R., Kuwabara H., Hesse S., Zessin J., Pawelke B., Stephan H., Bergmann R., Steinbach J. and Sabri O. (2003) In vivo measurement of the serotonin transporter with (S)-([18F]fluoromethyl)-(+)-McN5652. Neuropsychopharmacology 28, 2010-2019.
  • Friedrich A., Prasad P.D., Freyer D., Ganapathy V., Brust P. (2003) Molecular cloning and characterization of the OCTN2 transporter at the blood-brain barrier. Brain Res. 968, 69-79.
  • Brust P., Zessin J., Kuwabara H., Pawelke B., Kretzschmar M., Hinz R., Bergman J., Eskola O., Solin O., Steinbach J., Johannsen B. (2003) Positron emission tomography imaging of the serotonin transporter in the pig brain using [11C](+)-McN5652 and S-([18F]fluoromethyl)-(+)-McN5652. Synapse.47, 143-151.
  • Brust P.,Haubner R., Friedrich A., Scheunemann M., Anton M., Koufaki O.N., Hauses M., Noll S., Noll B., Haberkorn U., Schackert G., Schackert H.K., Avril N., Johannsen B. (2001) Comparison of [18F]FHPG and [124/125I]FIAU for imaging herpes simplex virus type 1 thymidine kinase gene expression. Eur. J. Nucl. Med. 28, 721-729.
  • Cumming P, Kretzschmar M, Brust P, Smith DF (2001) Quantitative radioluminography of serotonin uptake sites in the porcine brain. Synapse 39, 351-355.
  • Bauer R., Walter B, Vorwieger G, Bergmann R., Füchtner F., Brust P. (2001) Intrauterine growth restriction induces upregulation of AADC activity in newborn piglets - A [18F]Fluoro-DOPA -PET study. Pediat.Res. 49, 474-480.
  • Brust P., Friedrich A., Krizbai I.A., Bergmann R., Roux F., Ganapathy V., Johannsen B. (2000) Functional expression of the serotonin transporter in immortalized rat brain microvessel endothelial cells. J. Neurochem. 74, 1241-1248.
  • Brust P., Scheffel U., Szabo Z. (1999) Radioligands for the study of the 5-HT transporter in vivo. IDrugs 2, 129-145.
  • Srinivas P., Brust P., Subramanian A.R., Raghavan S.A.V., Rangisetty J.B., Gupta C.N.V.H.B., Parimoo P. (1999) Synthesis and preliminary binding affinities of 1-(1,2-dihydro-2-acenaphthylenyl) piperazine- a new arylpiperazine. Pharm. Acta Helv. 74, 73-76.
  • Brust P., Bauer R., Vorwieger G., Walter B., Bergmann R., Füchtner F., Steinbach J., Zwiener U., Johannnsen B. (1999) Upregulation of the aromatic amino acid decarboxylase under neonatal asphyxia. Neurobiol. Dis. 6, 131-139.
  • Hoepping A., Reisgys M., Brust P., Seifert S., Spies H., Alberto R., B. Johannsen (1998) TROTEC-1: A new high-affinity ligand for labeling of the dopamine transporter. J. Med. Chem. 41, 4429-4432.
  • Hoepping A., Brust P., Berger R., Spies H., Machill S., Scheller D., Johannsen B. (1998) Novel rhenium complexes derived from a-tropanole as potential ligands for the dopamine transporter Bioorg. Med. Chem. 6, 1663-1672.
  • Brust P., Bergmann R., Johannsen B. (1996) High-affinity binding of [3H]paroxetine to caudate nucleus and microvessels from porcine brain. Neuroreport 7, 1405-1408.
  • Brust P., Bech A., Kretzschmar R., Bergmann R. (1994) Developmental changes of enzymes involved in peptide degradation in isolated rat brain microvessels. Peptides 15, 1085-1088.
  • Ermisch A., Brust P., Kretzschmar R., Rühle H.-J. (1993) Peptides and blood-brain barrier transport. Physiol. Rev. 73, 489-527.
  • Brust P., Shaya E. K., Jeffries K. J., Dannals R. F., Ravert H. T., Wilson A. A., Conti P. S., Wagner H. N. Jr ., Gjedde A., Ermisch A., Wong D. F. (1992) Effects of vasopressin on blood-brain transfer of methionine in dogs. J. Neurochem. 59: 1421-1429.
  • Brust P., Christensen T., Diemer N. H. (1992) Decrease of extracellular taurine in the rat dorsal hippocampus after central nervous administration of vasopressin. J. Neurochem. 58, 1427-1431.
  • Brust P.,Baethmann A., Gjedde A., Ermisch A. (1991) Atrial natriuretic peptide augments the blood-brain transfer of water but not leucine and glucose. Brain Res.564, 91-96.
  • Brust P. (1986) Changes in regional blood-brain transfer of L-leucine elicited by arginine-vasopressin. J. Neurochem. 46:534-541.

Work Experience

InstitutionPeriodCountry
Helmholtz-Zentrum Dresden-Rossendorf
Institute of Radiopharmaceutical Cancer  Research
Research Site Leipzig (former IIF e.V.)
Department of Neuroradiopharmaceuticals, Head

at present,
since 2005

Germany
 
Institute of Interdisciplinary Isotope Research, Leipzig 
Senior scientist
2002 - 2005 Germany
 
Aarhus University, PET center Aarhus
Guest scientist
December 1996 Denmark
 
Senior scientist, Research Center Dresden-Rossendorf (HZDR) 1992-2001 Germany
 
Laboratory of Neurophysiology, NIMH, Bethesda
Guest scientist
November-December 1991 USA
 
Research Assistant, University of Leipzig, Institute of Biology 1991-1992 Germany
 
Department of Radiology, Johns Hopkins University
Guest scientist
January-June 1991 USA
 
Post-doc, McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University 1990-1991 Canada
 
Research Assistant, University of Leipzig, Institute of Biology 1986-1990 Germany
 
University of Copenhagen, Laboratory of Neuropathology; Guest scientist September-November 1988 Denmark
 
Academy of Sciences of the Czech Republik, Prague;
Guest scientist
May 1984 Czech Republik
 
University of Leipzig, Institute of Biology, Leipzig 1981 - 1986 Germany
 
University of Leipzig, Institute of Biology, Leipzig
Diploma in Biology
1976 - 1981 Germany

Memberships

  • German Society of Neurosciences NWG 
  • German Society of Nuclear Medicine DGN
  • Federation of European Neuroscience Societies FENS
  • International Brain Research Organization IBRO
  • European Society of Neurochemistry ESN