Song Zhendong, Li Yinlong, Dahl Kenneth, Chaudhary Ahmad, Sun Zhenkun, Zhou Xin, Chen Jiahui, Gao Yabiao, Rong Jian, Zhao Chunyu, Patel Jimmy S, Collier Lee, Ran Chongzhao, Zhai Chuangyan, Zhang Linqi, Haider Achi, Mühlfenzl Kim S, Yuan Hongjie, Elmore Charles S, Schou Magnus, Liang Steven H
Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, GA, 30322, USA.
PET Science Centre, Precision Medicine and Biosamples, Oncology R&D, AstraZeneca, Karolinska Institutet, Stockholm, Sweden.
Chembiochem. 2025 Feb 3;26(5):e202400655. doi: 10.1002/cbic.202400655. Epub 2024 Nov 4.
The histamine subtype 3 (H) receptor is an important drug target in the central nervous system (CNS), and PET imaging offers a promising technique for the noninvasive evaluation of CNS disease related to the H receptor. In this study, we synthesized and evaluated the binding effects of [F]H3-2404 and [F]H3-2405 by modifying the structure of AZD5213, a selective H antagonist. These two radioligands were prepared in high radiochemical yields and displayed stability in serum. The in vitro autoradiographic study in rat brain tissue and the following in vivo PET studies in mice demonstrated sufficient brain uptake but predominantly non-specific distribution in rodent brain. Although these data suggest that [F]H3-2404 and [F]H3-2405 are unsuitable as PET tracers for brain imaging of the H receptor, this study provides a valuable attempt for optimizing F labeled radiotracers based on AZD5213.
组胺3（H₃）受体是中枢神经系统（CNS）中的一个重要药物靶点，正电子发射断层扫描（PET）成像为无创评估与H₃受体相关的中枢神经系统疾病提供了一种很有前景的技术。在本研究中，我们通过修饰选择性H₃拮抗剂AZD5213的结构，合成并评估了[¹⁸F]H₃-2404和[¹⁸F]H₃-2405的结合效应。这两种放射性配体的制备具有很高的放射化学产率，并且在血清中表现出稳定性。在大鼠脑组织中进行的体外放射自显影研究以及随后在小鼠中进行的体内PET研究表明，它们在脑中摄取充足，但在啮齿动物脑中主要是非特异性分布。尽管这些数据表明[¹⁸F]H₃-2404和[¹⁸F]H₃-2405不适合作为用于H₃受体脑成像的PET示踪剂，但本研究为基于AZD5213优化¹⁸F标记的放射性示踪剂提供了一次有价值的尝试。
