Novel 18F-Labeled Benzimidazolone-Based Radioligands as Highly Selective Sigma-2 Receptor Probes for Tumor Imaging

被引：1

作者：

Wang, Jingqi ^{[1
]}

Wang, Tao ^{[1
]}

Mou, Tiantian ^{[2
]}

Yang, Tao ^{[3
]}

Gao, Xu ^{[1
]}

An, Xiaodan ^{[1
]}

Hu, Biao ^{[2
]}

Zhang, Jinming ^{[4
]}

Zhang, Xiaoli ^{[2
]}

Deuther-Conrad, Winnie ^{[5
]}

Huang, Yiyun ^{[6
]}

Jia, Hongmei ^{[1
]}

机构：

[1] Beijing Normal Univ, Coll Chem, Key Lab Radiopharmaceut, Minist Educ, Beijing 100875, Peoples R China

[2] Capital Med Univ, Beijing Anzhen Hosp, Dept Nucl Med, Beijing 100029, Peoples R China

[3] Capital Med Univ, Beijing Tiantan Hosp, Dept Tradit Chinese Med, Beijing 100070, Peoples R China

[4] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Nucl Med, Beijing 100853, Peoples R China

[5] Helmholtz Zentrum Dresden Rossendorf HZDR, Inst Radiopharmaceut Canc Res, Dept Neuroradiopharmaceut, D-04318 Leipzig, Germany

[6] Yale Univ, Sch Med, Yale PET Ctr, Dept Radiol & Biomed Imaging, New Haven, CT 06520 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2024年 / 67卷 / 19期

基金：

中国国家自然科学基金;

关键词：

P-GLYCOPROTEIN; BENZAMIDE ANALOGS; CYCLOSPORINE-A; BINDING-SITES; BRAIN; PROLIFERATION; EXPRESSION; CANCER; BLOOD; METABOLISM;

D O I：

10.1021/acs.jmedchem.4c01315

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel sigma-2 (sigma(2)) receptor ligands with benzimidazolone and 5,6-dimethoxyisoindoline as pharmacophores were designed and synthesized. Compound 4 exhibited low nanomolar affinity for the sigma(2 )receptors (K-i(sigma(2)) = 2.30 nM) and high subtype selectivity (K-i(sigma(1))/K-i(sigma(2)) > 1500). Radioligand [F-18]4 was prepared in radiochemical yields of 18 +/- 7%, with >99% radiochemical purity and molar activity of 244 +/- 136 GBq/mu mol. Biodistribution and blocking studies in mice and small animal PET/CT imaging in rats indicated highly specific binding of [F-18]4 in organs known to express the sigma(2) receptors. Small animal PET/CT imaging with [F-18]4 showed clear visualization of the tumors in subcutaneous A549 lung cancer and U87MG glioma xenografts, and intracranial orthotopic U87MG glioma models. Co-administration of CM398 with [F-18]4 significantly reduced activity uptake in the tumors, indicating that [F-18]4 specifically binds to the sigma(2) receptors expressed in A549 and U87MG xenografts.

引用

页码：17392 / 17406

页数：15

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