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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 [18F]FE@SNAP as a potential PET tracer for the MCHR1. Methods: [18F]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 [18F]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 [18F]FE@SNAP uptake was significantly blocked in the lateral hypothalamus, there is strong evidence that [18F]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 [18F]FE@SNAP could serve as a useful imaging and therapy monitoring tool for MCHR1-related pathologies.

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University of Vienna Phaidra  

Autor(es)

Philippe, Cécile -  Department fur Pharmazeutische Technologie und Biopharmazie, Fakultat fur Lebenswissenschaften, University of Vienna -  Haeusler, Daniela -  Division of Nuclear Medicine, Department of Biomedical Imaging and Image -  guided Therapy, Medical University of Vienna -  Scherer, Thomas -  Division of Endocrinology and Metabolism, Department of Medicine III, Medical University of Vienna -  Fürnsinn, Clemens -  Zeilinger, Markus -  Wadsak, Wolfgang -  Shanab, Karem -  Department fur Pharmazeutische Chemie, Fakultat fur Lebenswissenschaften, University of Vienna -  Spreitzer, Helmut -  Hacker, Marcus -  Mitterhauser, Markus - 

Id.: 69790065

Idioma: eng  - 

Versión: 1.0

Estado: Final

Tipo:  application/pdf -  2028543 bytes - 

Tipo de recurso: article  -  publishedVersion  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

: CC BY 4.0 International

Formatos:  application/pdf -  2028543 bytes - 

Requerimientos técnicos:  Browser: Any - 

Relación: [IsBasedOn] ISSN:2191-219X
[IsBasedOn] EJNMMI Research 6 (2016)

Fecha de contribución: 15-abr-2017

Contacto:

Localización:
* o:527629
* doi:10.1186/s13550-016-0186-7
* ISSN: 2191-219X
* hdl:11353/10.527629

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