Philippe_2013_Sci.Pharm_81_625

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 K d 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.