Article
Biochemistry & Molecular Biology
Thu Hang Lai, Magali Toussaint, Rodrigo Teodoro, Sladjana Dukic-Stefanovic, Mathias Kranz, Winnie Deuther-Conrad, Rares-Petru Moldovan, Peter Brust
Summary: The research focuses on developing a PET radiotracer for monitoring the expression and occupancy of the non-dopaminergic target A(2A) receptor in Parkinson's disease therapy. Novel fluorinated analogs are designed and evaluated in preclinical studies, showing specific in vitro binding to A(2A)R but no specific in vivo binding in dynamic PET/MRI studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Thu Hang Lai, Susann Schroeder, Magali Toussaint, Sladjana Dukic-Stefanovic, Mathias Kranz, Friedrich-Alexander Ludwig, Steffen Fischer, Joerg Steinbach, Winnie Deuther-Conrad, Peter Brust, Rares-Petru Moldovan
Summary: This study demonstrated the metabolic stability and specific binding of two fluorinated analogs as PET tracers in the brains of mice, with in vivo PET/MRI studies in CD-1 mice showing high initial brain uptake and rapid clearance for both radiotracers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Ying Zhang, Tao Wang, Xiaojun Zhang, Winnie Deuther-Conrad, Hualong Fu, Mengchao Cui, Jinming Zhang, Peter Brust, Yiyun Huang, Hongmei Jia
Summary: In this study, a series of indole-based derivatives were synthesized as novel sigma-2 receptor ligands, and two ligands with high affinity and selectivity were radiolabeled with F-18. Biodistribution studies in rodents showed that the radioligand [F-18]9 displayed high brain uptake and brain-to-blood ratio. Pre-treatment experiments and ex vivo autoradiography confirmed the specific binding of [F-18]9 to sigma-2 receptors in the brain. Dynamic positron emission tomography imaging further confirmed the regional distribution and specific binding of [F-18]9 in the rat brain.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Biochemistry & Molecular Biology
Xiang Zhang, Falguni Basuli, Zhen-Dan Shi, Swati Shah, Jianfeng Shi, Amelia Mitchell, Jianhao Lai, Zeping Wang, Dima A. Hammoud, Rolf E. Swenson
Summary: In this study, a series of fluorine-18-labeled L-rhamnose derivatives were developed as potential PET tracers for various fungal and bacterial strains. The tracer showed good stability and renal clearance in mice, with minimal tissue and skeletal uptake and a low background signal in healthy mice.
Review
Pharmacology & Pharmacy
Chao Wang, Rong Lin, Shaobo Yao
Summary: This review focuses on recent advances in the synthesis, radiolabeling, and application of a series of F-18-labeled amino acid analogs using new F-18-labeling strategies.
Review
Biochemistry & Molecular Biology
Felix Francis, Frank Wuest
Summary: Positron emission tomography (PET) is a vital imaging technique used for studying biological and physiological processes, with fluorine-18 (F-18) being a commonly used positron emitter in PET imaging. The presence of fluorine atoms in many drugs opens up possibilities for developing radioligands labeled with fluorine-18.
Article
Chemistry, Multidisciplinary
Tao Wang, Ying Zhang, Xiaojun Zhang, Leyuan Chen, Mingqiang Zheng, Jinming Zhang, Peter Brust, Winnie Deuther-Conrad, Yiyun Huang, Hongmei Jia
Summary: The study found that Racemic [F-18]FBFP is a potent sigma(1) receptor radiotracer with superior imaging properties. The two enantiomers showed comparable high affinity for sigma(1) receptors, with one behaving as an antagonist and the other as an agonist. In experimental tests on mice and rats, both enantiomers displayed good brain uptake and binding specificity.
CHINESE CHEMICAL LETTERS
(2022)
Article
Chemistry, Multidisciplinary
Chris Hoffmann, Niklas Kolks, Daniel Smets, Alexander Haseloer, Benedikt Groener, Elizaveta A. Urusova, Heike Endepols, Felix Neumaier, Uwe Ruschewitz, Axel Klein, Bernd Neumaier, Boris D. Zlatopolskiy
Summary: In this study, a series of complexes were systematically evaluated and several generally applicable mediators were identified for highly efficient radiofluorination. The utilization of these mediators significantly improved the labeling yields, even with lower precursor amounts. The practicality of the novel mediators was demonstrated by the efficient production of five PET tracers and transfer of the method to an automated radiosynthesis module.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Medicine, Research & Experimental
Hongzhang Yang, Lei Zhang, Huanhuan Liu, Yunming Zhang, Zhaobiao Mou, Xueyuan Chen, Jingchao Li, Fengming He, Zijing Li
Summary: 18F-labeled fluorothiophosphate (FTP) synthons with high radiochemical yields can be rapidly generated in reaction solutions using wet [18F]F- without the need for substrate pre-modification or lengthy radiosynthesis procedures. This simplified one-pot 18F-labeling method allows for the visualization and translation of a variety of biomolecules, making it valuable for modern positron emission tomography techniques.
Article
Medicine, Research & Experimental
Goncalo S. Clemente, Ines F. Antunes, Jurgen W. A. Sijbesma, Aren van Waarde, Adriaan A. Lammertsma, Alexander Domling, Philip H. Elsinga
Summary: PET studies with [F-18]atorvastatin in preclinical models revealed faster uptake and clearance in female rats compared to males, potentially due to higher efficiency in exchange between arterial blood and hepatic tissue.
MOLECULAR PHARMACEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Dario Fiorenza, Emanuele Nicolai, Carlo Cavaliere, Ferdinando Fiorino, Giovanna Esposito, Marco Salvatore
Summary: A novel fluorinated benzodiazepine ligand, [F-18]Fluoroethyltemazepam, was developed for positron emission tomography imaging of translocator protein (18 kDa). The radiolabelling was performed with an automated synthesizer, resulting in high radiochemical purity and yield. This automated procedure may serve as a basis for future production of [F-18]F-FETEM for preclinical PET imaging studies.
Article
Radiology, Nuclear Medicine & Medical Imaging
Thu Hang Lai, Magali Toussaint, Rodrigo Teodoro, Daniel Guendel, Friedrich-Alexander Ludwig, Barbara Wenzel, Susann Schroeder, Bernhard Sattler, Bjoern H. Falkenburger, Osama Sabri, Winnie Deuther-Conrad, Peter Brust, Sladjana Dukie-Stefanovie, Rare-Petru Moldovan
Summary: The study developed a metabolically stable radiotracer, [F-18]FLUDA, for the non-invasive imaging of the A(2A) receptor in the brain. Preclinical evaluation in mice and piglets showed high target specificity and low toxicity, indicating its readiness for human application in diagnosing and developing drugs targeting the A(2A) receptor.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Article
Chemistry, Multidisciplinary
Jay S. Wright, Richard Ma, E. William Webb, Wade P. Winton, Jenelle Stauff, Kevin Cheng, Allen F. Brooks, Melanie S. Sanford, Peter J. H. Scott
Summary: This report presents the development of a Zn(OTf)(2)-mediated method for converting alpha-tertiary haloamides to the corresponding alpha-tertiary fluoroamides. Under optimized conditions, high radiochemical conversion can be achieved. This method has been successfully applied to prepare various model radiofluorides.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Review
Biochemistry & Molecular Biology
Michael R. Kilbourn
Summary: The application of positron emission tomography (PET) imaging to study brain biochemistry, especially dopamine neurotransmission, has significantly grown over the past 40 years. PET imaging of dopaminergic functions in the central nervous system is routinely used for research in neurology, psychiatry, drug abuse and addiction, as well as drug development. The key advancement in PET imaging is the development of unique radiotracers labeled with positron-emitting radionuclides like carbon-11 and fluorine-18, which have greatly contributed to the progress in this field.
Article
Biochemistry & Molecular Biology
Guolong Huang, Xiaolei Lu, Yifan Qiu, Lei Bi, Peizhen Ye, Min Yang, Yanfang Shen, Hongjun Jin, Junbin Han
Summary: A novel P2X7R targeting radiotracer was synthesized and proved to stably retain and target P2X7R in vivo without defluorination in major organs. It shows potential as a promising PET radioligand for clinical translation.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)