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首页> 美国卫生研究院文献>Scientia Pharmaceutica >Preparation and First Preclinical Evaluation of 18FFE@SNAP: A Potential PET Tracer for the Melanin-Concentrating Hormone Receptor-1 (MCHR1)
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Preparation and First Preclinical Evaluation of 18FFE@SNAP: A Potential PET Tracer for the Melanin-Concentrating Hormone Receptor-1 (MCHR1)

机译：18F FE @ SNAP的制备和首次临床前评估：黑色素浓缩激素受体1（MCHR1）的潜在PET示踪剂。

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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.
机译：黑色素浓缩激素（MCH）系统是治疗人类疾病的新靶标。由于MCH系统涉及多种病理（肥胖，糖尿病和代谢反馈机制失调）的知识是基于体外或临床前研究的，因此需要开发合适的正电子发射断层扫描（PET）示踪剂。我们在此介绍[ 18 F] FE @ SNAP的制备和首次临床前评估-一种MCH受体-1（MCHR1）的新型PET示踪剂。使用微流体装置进行合成。临床前评估包括结合亲和力，血浆稳定性，血浆游离分数，对使用肝微粒体的细胞色素P-450（CYP450）系统的稳定性，对羧基酯酶的稳定性，以及评估血脑屏障（BBB）渗透的方法，例如作为logD分析和固定化人工膜（IAM）色谱。纯化后获得了374±202 MBq [ 18 F] FE @ SNAP的水平。获得的[ 18 F] FE @ SNAP的Kd值为2.9 nM。 [ 18 F] FE @ SNAP表现出对羧酸酯酶，CYP450酶和人体血浆的高稳定性。 LogD（3.83）和IAM色谱结果（Pm = 0.51）与已知的BBB穿透化合物在同一范围内。 [ 18 F] FE @ SNAP的合成是可靠和成功的。由于高结合亲和力和稳定性，[ 18 F] FE @ SNAP是MCHR1的有希望的示踪剂。

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