Synthesis and evaluation of a [18F]BODIPY-labeled caspase-inhibitor

被引：23

作者：

Ortmeyer, Christian Paul ^{[1
,2
]}

Haufe, Guenter ^{[2
,3
]}

Schwegmann, Katrin ^{[4
]}

Hermann, Sven ^{[4
]}

Schaefers, Michael ^{[1
,3
,4
]}

Boergel, Frederik ^{[5
]}

Wuensch, Bernhard ^{[5
]}

Wagner, Stefan ^{[1
]}

Hugenberg, Verena ^{[6
]}

机构：

[1] Univ Hosp Munster, Dept Nucl Med, Albert Schweitzer Campus 1,Bldg A1, D-48149 Munster, Germany

[2] Univ Munster, Organ Chem Inst, Corrensstr 40, D-48149 Munster, Germany

[3] Univ Munster, Cells In Mot Cluster Excellence, Waldeyerstr 15, D-48149 Munster, Germany

[4] Univ Munster, European Inst Mol Imaging, Waldeyerstr 15, D-48149 Munster, Germany

[5] Univ Munster, Inst Pharmaceut & Med Chem, Corrensstr 48, D-48149 Munster, Germany

[6] HDZ NRW, Inst Radiol Nucl Med & Mol Imaging, Georgstr 11, D-32545 Bad Oeynhausen, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2017年 / 25卷 / 07期

关键词：

BODIPY; Caspase inhibitor; Molecular Imaging; F-18-labeling; Dual-labeled probe; RADIOLABELED ISATIN ANALOGS; BODIPY DYES; IN-VITRO; SULFONAMIDE ANALOGS; APOPTOSIS; POTENT; DERIVATIVES; ACTIVATION; BORON; PET;

D O I：

10.1016/j.bmc.2017.02.033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

BODIPYs (boron dipyrromethenes) are fluorescent dyes which show high stability and quantum yields. They feature the possibility of selective F-18-fluorination at the boron-core. Attached to a bioactive molecule and labeled with [F-18]fluorine, the resulting compounds are promising tracers for multimodal imaging in vivo and can be used for PET and fluorescence imaging. A BODIPY containing a phenyl and a hydroxy substituent on boron was synthesized and characterized. Fluorinated and hydroxy substituted dyes were coupled to an isatin-based caspase inhibitor via cycloaddition and the resulting compounds were evaluated in vitro in caspase inhibition assays. The metabolic stability and the formed metabolites were investigated by incubation with mouse liver microsomes and LC-MS analysis. Subsequently the fluorophores were labeled with [F-18]fluorine and an in vivo biodistribution study using dynamic PET was performed. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：2167 / 2176

页数：10

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