Synthesis and in vitro evaluation of new translocator protein ligands designed for positron emission tomography

被引：5
作者：
Kalina, Thomas [1 ]
Berroteran-Infante, Neydher [2 ,3 ]
Schmitl, Stefan [2 ]
Vraka, Chrysoula [2 ]
Hacker, Marcus [2 ]
Mitterhauser, Markus [2 ,4 ,5 ]
Pallitsch, Katharina [1 ]
Wadsak, Wolfgang [2 ,3 ,6 ]
机构：
[1] Univ Vienna, Dept Organ Chem, Fac Chem, Vienna, Austria
[2] Med Univ Vienna, Div Nucl Med, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria
[3] Univ Vienna, Dept Inorgan Chem, Fac Chem, Vienna, Austria
[4] Univ Vienna, Fac Life Sci, Dept Pharmaceut Technol, Vienna, Austria
[5] Ludwig Boltzmann Inst Appl Diagnost, Vienna, Austria
[6] CBmed GmbH, Ctr Biomarker Res Med, Graz, Austria
来源：
FUTURE MEDICINAL CHEMISTRY | 2019年 / 11卷 / 06期
关键词：
PET; polymorphism rs6971; preclinical evaluation; radiosynthesis; synthesis; TSPO; PERIPHERAL BENZODIAZEPINE-RECEPTOR; 18; KDA; PET RADIOLIGANDS; AFFINITY BINDING; PRIMARY AMINES; TSPO; BRAIN; POLYMORPHISM; SENSITIVITY; ACTIVATION;
D O I：
10.4155/fmc-2018-0444
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Aim: Dysregulated levels of the translocator protein TSPO18KDa have been reported in several disorders, particularly neurodegenerative diseases. This makes TSPO an interesting target for the development of diagnostic biomarkers. Even though several radioligands have already been developed for in vivo TSPO imaging, the ideal TSPO radiotracer has still not been found. Results: Here, we report the chemical synthesis of a set of new TSPO ligands designed for future application in positron emission tomography, together with the determination of their biological activity and applied C-11-labeling strategy. Conclusion: The lead compound of our series, (R)-[C-11]Me@NEBIQUINIDE, showed very promising results and is therefore proposed to be further evaluated under in vivo settings.
引用
收藏
页码：539 / 550
页数：12
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