title: [(18)F]FE@SNAP-a specific PET tracer for melanin-concentrating hormone receptor 1 imaging?
abstract: BACKGROUND
  The melanin-concentrating hormone receptor 1 (MCHR1), which is highly expressed in the lateral hypothalamus, plays a key role in energy homeostasis, obesity and other endocrine diseases. Hence, there is a major interest in in vivo imaging of this receptor. A PET tracer would allow non-invasive in vivo visualization and quantification of the MCHR1. The aim of the study was the ex vivo evaluation of the MCHR1 ligand [(18)F]FE@SNAP as a potential PET tracer for the MCHR1.
  
  
  METHODS
  [(18)F]FE@SNAP was injected directly into the jugular vein of awake naïve rats for ex vivo brain autoradiography, biodistribution and additional blood metabolite analysis. Blocking experiments were conducted using the unlabeled MCHR1 ligand SNAP-7941.
  
  
  RESULTS
  A high uptake of [(18)F]FE@SNAP was observed in the lateral hypothalamus and the ventricular system. Both regions were significantly blocked by SNAP-7941. Biodistribution evinced the highest uptake in the kidneys, adrenals, lung and duodenum. Specific blocking with SNAP-7941 led to a significant tracer reduction in the heart and adrenals. In plasma samples, 47.73 ± 6.1 % of a hydrophilic radioactive metabolite was found 45 min after tracer injection.
  
  
  CONCLUSIONS
  Since [(18)F]FE@SNAP uptake was significantly blocked in the lateral hypothalamus, there is strong evidence that [(18)F]FE@SNAP is a highly suitable agent for specific MCHR1 imaging in the central nervous system. Additionally, this finding is supported by the specific blocking in the ventricular system, where the MCHR1 is expressed in the ependymal cells. These findings suggest that [(18)F]FE@SNAP could serve as a useful imaging and therapy monitoring tool for MCHR1-related pathologies.
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.|Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria.
authors.forename: Cécile
authors.initials: C
authors.lastname: Philippe
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Haeusler
authors.affiliation: Department of Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Scherer
authors.affiliation: Department of Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna, Vienna, Austria.
authors.forename: Clemens
authors.initials: C
authors.lastname: Fürnsinn
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Zeilinger
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Karem
authors.initials: K
authors.lastname: Shanab
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Vienna, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Spreitzer
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Marcus
authors.initials: M
authors.lastname: Hacker
authors.affiliation: Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria. markus.mitterhauser@meduniwien.ac.at.|Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria. markus.mitterhauser@meduniwien.ac.at.|Ludwig Boltzmann Institute for Applied Diagnostics, Vienna, Austria. markus.mitterhauser@meduniwien.ac.at.
authors.forename: Markus
authors.identifier: http://orcid.org/0000-0003-3173-5272
authors.initials: M
authors.lastname: Mitterhauser
keywords: Autoradiography; Imaging; In vivo; MCHR1; [18F]FE@SNAP