Institute of Radiopharmaceutical Cancer Research, Department of Neuroradiopharmaceuticals, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Research Site Leipzig, 04318 Leipzig, Germany.
Department of Research and Development, ROTOP Pharmaka GmbH, 01069 Dresden, Germany.
J Med Chem. 2022 Jul 14;65(13):9034-9049. doi: 10.1021/acs.jmedchem.2c00256. Epub 2022 Jun 30.
The cannabinoid receptor type 2 (CB2R) is an attractive target for the diagnosis and therapy of neurodegenerative diseases and cancer. In this study, we aimed at the development of a novel F-labeled radioligand starting from the structure of the known naphthyrid-2-one CB2R ligands. Compound () was identified with the highest binding affinity and selectivity versus CB1R (CB2R = 0.6 nM; CB1R/CB2R > 1000) and was selected for radiolabeling with fluorine-18 and biological characterization. The new radioligand showed high CB2R affinity in vitro as well as high metabolic stability in vivo. PET imaging with in a rat model of vector-based/-related hCB2R overexpression in the striatum revealed a high signal-to-background ratio. Thus, is a novel and highly promising PET radioligand for the imaging of upregulated CB2R expression under pathological conditions in the brain.
大麻素受体 2 型（CB2R）是诊断和治疗神经退行性疾病和癌症的有吸引力的靶点。在这项研究中，我们旨在从已知的萘啶-2-酮 CB2R 配体的结构出发，开发一种新型 F 标记放射性配体。化合物 () 被鉴定为具有最高的结合亲和力和选择性，对 CB1R（CB2R = 0.6 nM；CB1R/CB2R > 1000），并被选择用于氟-18 标记和生物学特征分析。新型放射性配体 在体外显示出高 CB2R 亲和力，体内代谢稳定性高。在纹状体中基于载体的/hCB2R 过表达的大鼠模型中，用 进行 PET 成像显示出高的信号与背景比。因此， 是一种新型的、很有前途的用于在大脑病理条件下成像上调的 CB2R 表达的 PET 放射性配体。
