title: Preclinical in vitro &in vivo evaluation of [(11)C]SNAP-7941 - the first PET tracer for the melanin concentrating hormone receptor 1.
abstract: BACKGROUND
  Due to its involvement in a variety of pathologies (obesity, diabetes, gut inflammation and depression), the melanin concentrating hormone receptor 1 (MCHR1) is a new target for the treatment of these lifestyle diseases. We previously presented the radiosynthesis of [(11)C]SNAP-7941, the first potential PET tracer for the MCHR1.
  
  
  METHODS
  We herein present its in vitro and in vivo evaluation, including binding affinity, plasma stability, stability against liver mircrosomes and carboxylesterase, lipohilicity, biodistribution, in vivo metabolism and small-animal PET.
  
  
  RESULTS
  [(11)C]SNAP-7941 evinced high stability against liver microsomes, carboxylesterase and in human plasma. The first small-animal PET experiments revealed a 5 fold increased brain uptake after Pgp/BCRP inhibition. Therefore, it can be assumed that [(11)C]SNAP-7941 is a Pgp/BCRP substrate. No metabolites were found in brain.
  
  
  CONCLUSIONS
  On the basis of these experiments with healthy rats, the suitability of [(11)C]SNAP-7941 for the visualisation of central and peripheral MCHR1 remains speculative.
authors.affiliation: Radiochemistry and Biomarker Development Unit, Department of Nuclear Medicine, Medical University of Vienna, Vienna, Austria; Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna, Austria.
authors.forename: Cécile
authors.initials: C
authors.lastname: Philippe
authors.forename: Lukas
authors.initials: L
authors.lastname: Nics
authors.forename: Markus
authors.initials: M
authors.lastname: Zeilinger
authors.forename: Claudia
authors.initials: C
authors.lastname: Kuntner
authors.forename: Thomas
authors.initials: T
authors.lastname: Wanek
authors.forename: Severin
authors.initials: S
authors.lastname: Mairinger
authors.forename: Karem
authors.initials: K
authors.lastname: Shanab
authors.forename: Helmut
authors.initials: H
authors.lastname: Spreitzer
authors.forename: Helmut
authors.initials: H
authors.lastname: Viernstein
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D004355:Drug Stability; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D010880:Piperidines / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011743:Pyrimidines / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; C491208:MCHR1 protein, rat; D010880:Piperidines; D011743:Pyrimidines; D017481:Receptors, Somatostatin; C464854:SNAP7941; D002265:Carboxylic Ester Hydrolases
keywords: MCHR1; Metabolites; PET; SNAP-7941