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Sci. Pharm. 2013, 81(3), 625-640; doi:10.3797/scipharm.1306-02

Preparation and First Preclinical Evaluation of [18F]FE@SNAP: A Potential PET Tracer for the Melanin-Concentrating Hormone Receptor-1 (MCHR1)

1
Radiochemistry and Biomarker Development Unit, Department of Nuclear Medicine, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria
2
Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, 1090 Vienna, Austria
3
Department of Nutritional Sciences, University of Vienna, Althanstraße 14, 1090 Vienna, Austria
4
Department of Drug and Natural Product Synthesis, University of Vienna, Althanstraße 14, 1090 Vienna, Austria
5
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Waehringer Guertel 18–20, 1090 Vienna, Austria
6
Department of Inorganic Chemistry, University of Vienna, Waehringer Straße 42, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Received: 3 June 2013 / Accepted: 1 July 2013 / Published: 1 July 2013
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Abstract

The melanin-concentrating hormone (MCH) system is a new target for the treatment of human disorders. Since the knowledge of the MCH system's involvement in a variety of pathologies (obesity, diabetes, and deregulation of metabolic feedback mechanism) is based on in vitro or preclinical studies, a suitable positron emission tomography (PET) tracer needs to be developed. We herein present the preparation and first preclinical evaluation of [18F]FE@SNAP – a new PET tracer for MCH receptor-1 (MCHR1). The synthesis was performed using a microfluidic device. Preclinical evaluation included binding affinity, plasma stability, plasma free fraction, stability against the cytochrome P-450 (CYP450) system using liver microsomes, stability against carboxyl-esterase, and methods to assess the penetration of the blood-brain barrier (BBB) such as logD analysis and immobilized artificial membrane (IAM) chromatography. Levels at 374 ± 202 MBq [18F]FE@SNAP were obtained after purification. The obtained Kd value of [18F]FE@SNAP was 2.9 nM. [18F]FE@SNAP evinced high stability against carboxylesterase, CYP450 enzymes, and in human plasma. LogD (3.83) and IAM chromatography results (Pm=0.51) were in the same range as for known BBB-penetrating compounds. The synthesis of [18F]FE@SNAP was reliable and successful. Due to high binding affinity and stability, [18F]FE@SNAP is a promising tracer for MCHR1.
Keywords: MCHR1; Fluorine-18; PET; SNAP-7941; Radioligand MCHR1; Fluorine-18; PET; SNAP-7941; Radioligand
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

PHILIPPE, C.; NICS, L.; ZEILINGER, M.; SCHIRMER, E.; SPREITZER, H.; KARANIKAS, G.; LANZENBERGER, R.; VIERNSTEIN, H.; WADSAK, W.; MITTERHAUSER, M. Preparation and First Preclinical Evaluation of [18F]FE@SNAP: A Potential PET Tracer for the Melanin-Concentrating Hormone Receptor-1 (MCHR1). Sci. Pharm. 2013, 81, 625-640.

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