A benzenesulfonamide derivative as a novel PET radioligand for CXCR4.
A benzenesulfonamide derivative as a novel PET radioligand for CXCR4.
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苯磺酰胺衍生物作为 CXCR4 的新型 PET 放射性配体。
DOI：
10.1016/j.bmc.2019.115240
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发表时间：
2020
影响因子：
3.5
通讯作者：
Shim,Hyunsuk
中科院分区：
文献类型：
--
作者：
Oum,YoonHyeun;Shetty,Dinesh;Yoon,Younghyoun;Liang,Zhongxing;Voll,RonaldJ;Goodman,MarkM;Shim,Hyunsuk
CXCR 4通过与其天然内源性配体趋化因子CXCL 12相互作用参与多种疾病，如炎症、肿瘤生长和癌症转移。为了开发CXCR 4的成像探针，我们开发了一种新的小分子CXCR 4靶向PET剂（化合物5），通过点击化学将我们建立的苯磺酰胺支架与标记组分相结合。5显示出对已知CXCR 4拮抗剂（TN 14003）的纳摩尔亲和力（IC 50 = 6.9 nM），并在体外测定中抑制10 nM的65%以上的趋化性。放射性氟化化合物5（[18F]5）以剂量依赖性方式显示针对CXCL 12的竞争性细胞摄取。此外，[18 F] 5的microPET图像在λ-角叉菜胶诱导的爪水肿、人头颈癌原位异种移植物和每种小鼠模型的转移性肺癌的病变中表现出放射性的优先蓄积。
CXCR4 is involved in various diseases such as inflammation, tumor growth, and cancer metastasis through the interaction with its natural endogenous ligand, chemokine CXCL12. In an effort to develop imaging probes for CXCR4, we developed a novel small molecule CXCR4-targeted PET agent (compound5)by combining our established benzenesulfonamide scaffold with a labeling component by virtue of click chemistry.5shows nanomolar affinity (IC50= 6.9 nM) against a known CXCR4 antagonist (TN14003) and inhibits more than 65% chemotaxis at 10 nM in vitro assays. Radiofluorinated compound5([18F]5) demonstrates a competitive cellular uptake against CXCL12 in a dose-dependent manner. Further, microPET images of [18F]5exhibits preferential accumulation of radioactivity in the lesions of λ-carrageenan-induced paw edema, human head and neck cancer orthotopic xenograft, and metastatic lung cancer of each mouse model.