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The MCHR1 is an interesting pharmacological and pharmaceutical target, due to its involvement in pathologies as diabetes, gut inflammation and adiposity. in vivo PET-studies of the MCHR1 in energy homeostasis and diabetes could be of great value for deeper understanding of endocrinological hormone status and consequential pharmacological interactions. Furthermore, PET-tracers would facilitate compound dose selection of MCHR1 antagonists for treatment. Therefore, we developed two potential PET-tracers, [(11)C]SNAP-7941 and [(18)F]FE@SNAP, for the in vivo visualization of this receptor. Aim of this study was a preclinical in vitro evaluation of both unlabeled ligands. Therefore, a comparative autoradiographic investigation on CNS (coronal rat brain and 4 different human brain regions) and peripheral tissues (rat tongue as target and rat testes as non-target region) was conducted. Competition experiments, using the two radioligands [(125)I]-MCH and [(125)I]-S36057, were performed with selective and specific MCHR1 ligands as PMC-3886, a MCHR1 agonist, SNAP-7941 and FE@SNAP, two MCHR1 antagonists. Additionally, immunohistochemical staining with a specific MCHR1 antibody was performed. Specific binding was found in all tissues known to express the MCHR1 as human and rat CNS and peripheral rat tongue tissue. No specific binding was found in the non-target region of rat testes. MCHR1 antibody staining complemented the outcome of the autoradiographic experiments. The compounds SNAP-7941 and FE@SNAP were generally comparable with PMC-3886. Hence, the in vitro autoradiographic study of the unlabeled compounds SNAP-7941 and FE@SNAP further qualifies the potential of the PET-tracers [(11)C]SNAP-7941 and [(18)F]FE@SNAP as useful MCHR1 PET-tracers., (Copyright © 2014 Elsevier B.V. All rights reserved.)