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第一个GPR119PET成像联体:合成,放射化学和初步评估

Avinash H Bansode¹, Naresh Damuka¹, Nagaraju Bashetti²

¹Department of Radiology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, United States.

Journal of medicinal chemistry

|June 14, 2023

概括

一种新的正电子发射断层扫描 (PET) 追踪器[18F]KSS3已经开发出来,可以在体内可视化G蛋白结合受体119 (GPR119). 这种追踪器显示了推动GPR119向糖尿病药物开发的前景.

科学领域:

药理学药理学是指药理学的学科.
放射化学放射化学是指辐射化学.
分子成像学分子成像学

背景情况:

G蛋白结合受体119 (GPR119) 是2型糖尿病治疗的关键标,影响葡萄糖平衡,食欲和体重.
目前对GPR119激动剂的药物开发缺乏用于目标参与和分布研究的体内成像工具.

研究的目的:

为了合成和评估一种新的正子发射断层扫描 (PET) 放射追踪器[18F]KSS3,用于在体内成像GPR119的.
评估[18F]KSS3在针对2型糖尿病的GPR119的药物开发策略中的潜力.

主要方法:

[18F]KSS3.3的合成和放射性标记
在实验室中进行细胞吸收研究,并在动物中进行体内/体外生物分布研究.
在动物中使用非放射性KSS3和PET成像进行阻断研究.

主要成果:

[18F]KSS3表现出高放射性化学纯度和特定活性.
在富含GPR119的组织如胰腺,肝脏和肠道中观察到显著的吸收.
阻断研究证实了[18F]KSS3对胰腺GPR119的特异性.

结论:

[18F]KSS3是一种有前途的新型PET放射追踪器,用于成像GPR119.
这种标记物可以促进GPR119治疗2型糖尿病的药物开发,通过启用体内目标参与研究.

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