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Porträt Prof. Dr. Brust, Peter; FWPN

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

[18F]NCFHEB/[18F]Flubatine a potential PET marker of early Alzheimer`s disease


The nicotinic α4β2 acetylcholine receptor is an important target for diagnostic neuroimaging and drug development because of its involvement in learning and memory processes, neuropsychiatric diseases such as Alzheimer´s disease, Parkinsons´s disease, Tourette´s syndrome, epilepsy, autism, attention-deficit hyperactivity disorder, schizophrenia, and depression, as well as drug addiction and pain. In our group, highly affine and selective α4β2 nAChR targeting radiotracers have been developed which are related to the structure of the alkaloid epibatidine. The two radiolabeled enantiomers of norchloro-fluoro-homoepibatidine (NCFHEB), (+)-[18F]flubatine and (-)-[18F]flubatine, were investigated in piglets in dynamic PET studies. (-)-[18F]flubatine proofed to possess radiotracer properties superior to the clinically used 2-[18F]F-A85380, and was already assessed in man to quantitatively image α4β2nAChR in the living brain. The other enantiomer (+)-[18F]flubatine is currently also under investigation in patients with Alzheimer´s disease.

     
flubatine_preclincal_clinical

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Partners

  • Department of Nuclear Medicine and Department of Psychiatry, University of Leipzig

  • Central Institute for Electronics, Research Center Juelich

  • Advanced Biochemical Compounds ABX GmbH, Radeberg

Publications

  • Kranz M, Sattler B, Tiepolt S., Deuther-Conrad W, Donat C.K., Fischer S, Patt M, Schildan A., Patt J., Smits R, Hoepping A, Steinbach J., Sabri O., Brust P. Image based internal dosimetry of (+)-[18F]flubatine, comparing preclinical PET/MRI and PET/CT to first-in-human PET/CT results. Eur J Nucl Med Molec Imaging Physics. 2016, 3, 25.
  • Ludwig FA, Smits R, Fischer S, Donat CK, Hoepping A, Brust P, Steinbach J. LC-MS Supported Studies on the in Vitro Metabolism of both Enantiomers of Flubatine and the in Vivo Metabolism of (+)-[18F] Flubatine—A Positron Emission Tomography Radioligand for Imaging α4β2 Nicotinic Acetylcholine Receptors. Molecules. 2016, 21(9), 1200.
  • Sabri O, Becker  GA, Meyer PM, Hesse S, Wilke S, Graef S., Patt M, Luthardt J, Wagenknecht G, Hoepping A, Smits R, Franke A, Sattler B, Habermann B, Neuhaus P, Fischer S, Tiepolt S, Deuther-Conrad W, Barthel H, Schönknecht P, Brust P. First-in-human PET quantification study of cerebral α4β2 nicotinic acetylcholine receptors using the novel specific radioligand (-)-[18F]Flubatine. Neuroimage. 2015, 118:199-208.
  • Sattler B, Kranz M, Starke A, Wilke S, Donat CK, Deuther-Conrad W, Patt M, Schildan A, Patt J, Smits R, Hoepping A, Schönknecht P, Steinbach J, Brust P, Sabri O. Internal dose assessment of (–)-[18F]flubatine, comparing animal model data sets of mice and piglets with first-in-man results. J Nucl Med.2014, 55, 1885-1892.
  • Patt M, Becker, GA, Grossmann U, Habermann B, Schildan A, Wilke S, Deuther-Conrad W, Graef S, Fischer S, Hiller A, Smits R, Hoepping A, Wagenknecht G, Steinbach J, Gertz HJ, Hesse S, Schönknecht P, Brust P, Sabri O. Evaluation of metabolism, plasma protein binding and other biological parameters after administration of (-)-[18F]flubatine in humans. Nucl Med. Biol. 2014, 41, 489–494.
  • Smits R, Fischer S, Hiller A, Deuther-Conrad W, Cumming P, 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. Bioorg Med Chem. 2014, 22: 804-812.
  • 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. Appl. Radiat. Isot. 2013, 80: 7-11
  • 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 of α4β2 nicotinic acetylcholine receptors. Appl. Radiat. Isot. 2013, 74, 128-136.
  • Meyer PM, 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. Reduced alpha4beta2*-nicotinic acetylcholine receptor binding and its relationship to mild cognitive and depressive symptoms in Parkinson disease. Arch Gen Psychiatry. 2009,66(8):866-77.

  • Brust P, Patt JT, 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. 2008,62(3):205-18.

  • Deuther-Conrad W, Patt JT, Lockman PR, Allen DD, Patt M, Schildan A, Ganapathy V, Steinbach J, Sabri O, Brust P. Norchloro-fluoro-homoepibatidine (NCFHEB) - a promising radioligand for neuroimaging nicotinic acetylcholine receptors with PET. Eur Neuropsychopharmacol. 2008,18(3):222-9.

Financial support by

  • Deutsche Forschungsgemeinschaft - DFG
  • Federal Ministry of Education and Research
  • Helmholtz Validation Fonds

Contact

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