Article
Chemistry, Multidisciplinary
Melissa Chasse, Anna Pees, Anton Lindberg, Steven H. H. Liang, Neil Vasdev
Summary: Positron emission tomography (PET) is a powerful imaging tool used for drug discovery, clinical diagnosis, and disease monitoring. However, the lack of compatible methods and precursors for radiolabeling with fluorine-18 has limited the development of radiotracers. The radiolabeling of electron-rich (hetero)aromatic rings has been a long-standing challenge in producing PET radiopharmaceuticals. In this personal account, the history and applications of spirocyclic iodonium ylide precursors are discussed for the incorporation of fluorine-18 into complex non-activated (hetero)aromatic rings.
Article
Chemistry, Organic
Keitaro Matsuoka, Honoka Obata, Kotaro Nagatsu, Masahiro Kojima, Tatsuhiko Yoshino, Mikako Ogawa, Shigeki Matsunaga
Summary: The transition-metal-free At-211-astatination method described involves the nucleophilic aromatic substitution reaction of spirocyclic aryliodonium ylides, resulting in good to excellent radiochemical yields of At-211-radiolabeled compounds derived from multi-functionalized molecules and heteroarenes.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Jae-Hoon Lee, Fabrice G. Sime, Jeih-San Liow, Cheryl L. Morse, Robert L. Gladding, Jose A. Montero Santamaria, Ioline D. Henter, Sami S. Zoghbi, Victor W. Pike, Robert B. Innis
Summary: This study developed an F-18-labeled TSPO PET radioligand based on ER176 and evaluated its performance in the monkey brain. The most promising candidates were selected based on specific/nondisplaceable uptake ratio and time stability of total distribution volume.
JOURNAL OF NUCLEAR MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Viktor A. A. Il'in, Elena V. V. Pyzhik, Anton B. Balakhonov, Maksim A. A. Kiryushin, Evgeniya V. V. Shcherbatova, Andrey A. A. Kuznetsov, Pavel A. A. Kostin, Andrey V. V. Golovin, Vladimir A. A. Korshun, Vladimir A. A. Brylev, Kseniya A. A. Sapozhnikova, Alexey M. M. Kopylov, Galina V. V. Pavlova, Igor N. N. Pronin
Summary: Central nervous system tumors related to gliomas account for about 30% of all primary brain tumors. Surgical attack is the main treatment approach as there is no effective therapy for glioma. The use of PET imaging methods, such as positron emission tomography, can enhance the accuracy of glioma removal by distinguishing malignant tissue. However, PET lacks specific visualization of cells with certain molecular markers. In this study, aptamers were used to enhance specificity in imaging tumor cells bearing the epidermal growth factor receptor (EGFR). Conjugates of aptamers specific to EGFR were successfully obtained and can be used for further PET analysis on model animals with grafted glioblastoma.
Article
Critical Care Medicine
Daniel C. Schroeder, Erik Popp, Cathrin Rohleder, Stefanie Vus, David de la Puente Bethencourt, Simon R. Finke, Boris D. Zlatopolskiy, Johannes Zischler, Alexander Drzezga, Holger Herff, Thorsten Annecke, Tim Hucho, Bernd Neumaier, Bernd W. Boettiger, Heike Endepols
Summary: Neuroinflammation mediated by TSPO-expressing cells persists long-term after sudden cardiac arrest, potentially impacting cognitive functions. PET imaging and immunohistochemistry confirmed significant accumulation of TSPO in brain regions such as the dorsal hippocampus and striatum.
Review
Chemistry, Medicinal
Anupriya Adhikari, Ming-Rong Zhang, Anjani Kumar Tiwari
Summary: This review summarizes the recent advancements in ABO derivatives as the next generation TSPO PET ligands for neuroinflammation imaging, emphasizing on the crucial structural features responsible for visualizing TSPO in-vivo, with a compilation of published reports in the last 10 years.
DRUG DEVELOPMENT RESEARCH
(2022)
Review
Medicine, Research & Experimental
Anupriya Adhikari, Priya Singh, Kamalesh S. Mahar, Manish Adhikari, Bhawana Adhikari, Ming-Rong Zhang, Anjani Kumar Tiwari
Summary: TSPO is utilized as a potential biomarker for peripheral sterile inflammatory diseases (PSIDs), aiding in characterization and localization of inflammatory foci for proper therapy. As an important biological marker in PET imaging, TSPO has significant applications in oncology and PSIDs.
MOLECULAR PHARMACEUTICS
(2021)
Article
Neurosciences
Xiang Kong, Song Luo, Yun Fei Wang, Gui Fen Yang, Guang Ming Lu, Long Jiang Zhang
Summary: Neuroinflammation is a key factor in the pathogenesis of hepatic encephalopathy, with TSPO upregulation providing a molecular target for imaging. The study using BDL rats found that both [18F]PBR146 and [18F]DPA-714 can quantitatively evaluate neuroinflammation in hepatic encephalopathy models, with specific brain regions showing abnormal uptake and correlating with behavioral alterations.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Biotechnology & Applied Microbiology
Xue Xue, Rui Duan, Guoyan Zheng, Hucheng Chen, Weiwei Zhang, Liang Shi
Summary: This study investigates the role of translocator protein (TSPO) in the phenotypic transformation of microglia in Parkinson's disease (PD) and suggests a potential therapeutic role for TSPO in PD treatment.
Article
Pharmacology & Pharmacy
Zhiwei Xiao, Huiyi Wei, Yi Xu, Ahmed Haider, Junjie Wei, Shiyu Yuan, Jian Rong, Chunyu Zhao, Guocong Li, Weibin Zhang, Huangcan Chen, Yuefeng Li, Lingling Zhang, Jiyun Sun, Shaojuan Zhang, Hai-Bin Luo, Sen Yan, Qijun Cai, Lu Hou, Chao Che, Steven H. Liang, Lu Wang
Summary: A novel 18F-aryl PDE10A PET radioligand, [18F]9, was designed and synthesized in this study. The radioligand showed good in vitro binding affinity and selectivity towards PDE10A, as well as reasonable lipophilicity and brain permeability. PET imaging studies revealed high striatal uptake and excellent in vivo specificity. Preclinical studies in rodents confirmed the improved stability of [18F]9 compared to the current reference standard. Overall, [18F]9 is considered a promising PDE10A PET radioligand for clinical translation.
ACTA PHARMACEUTICA SINICA B
(2022)
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
Radiology, Nuclear Medicine & Medical Imaging
Nisha K. Ramakrishnan, Matthew Hird, Stephen Thompson, David J. Williamson, Luxi Qiao, David R. Owen, Allen F. Brooks, Peter J. H. Scott, Sergio Bacallado, John T. O'Brien, Franklin Aigbirhio
Summary: This study evaluated the two enantiomers of [F-18]GE387, showing that (S)-[F-18]GE387 has favorable kinetics in healthy subjects and can distinguish inflamed brain regions in neuroinflammation models, while also demonstrating low sensitivity to TSPO polymorphism in human brain tissue.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Article
Anesthesiology
Christina Mueller, Yu-Hua D. Fang, Chloe Jones, Jonathan E. Mcconathy, Fabio Raman, Suzanne E. Lapi, Jarred W. Younger
Summary: This study found increased binding of the translocator protein radioligand in several brain regions among fibromyalgia patients. The results suggest that individuals with fibromyalgia may have higher levels of neuroinflammation than healthy controls. Additionally, the study found higher binding levels in multiple brain regions among high-affinity binders in the fibromyalgia group. The differences in the right parietal gray matter were associated with decreased quality of life, higher pain severity and interference, and cognitive problems.
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.
Review
Biochemistry & Molecular Biology
Chiara Tremolanti, Lorenzo Germelli, Elisabetta Barresi, Eleonora Da Pozzo, Francesca Simorini, Sabrina Castellano, Sabrina Taliani, Federico Da Settimo, Claudia Martini, Barbara Costa
Summary: Neuroinflammation is a defense mechanism in the nervous system, but improper regulation can lead to neurodegenerative diseases. TSPO, an overexpressed protein in neuroinflammation and neurodegenerative diseases, has potential in promoting neuroprotection. This review summarizes the potential effects of TSPO on neuroinflammation and related mechanisms.
CURRENT MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Kuan Hu, Jingjie Shang, Lin Xie, Masayuki Hanyu, Yiding Zhang, Zhimin Yang, Hao Xu, Lu Wang, Ming-Rong Zhang
Article
Chemistry, Multidisciplinary
Ji-yun Sun, Katsushi Kumata, Zhen Chen, Yi-ding Zhang, Jia-hui Chen, Akiko Hatori, Hua-long Fu, Jian Rong, Xiao-yun Deng, Tomoteru Yamasaki, Lin Xie, Kuan Hu, Masayuki Fujinaga, Qing-zhen Yu, Tuo Shao, Thomas Lee Collier, Lee Josephson, Yi-han Shao, Yun-fei Du, Lu Wang, Hao Xu, Ming-rong Zhang, Steven H. Liang
Summary: N-methyl-D-aspartate receptors (NMDARs) play important roles in the CNS, with GluN2B being a well-studied subtype. Two GluN2B-selective negative allosteric modulators were synthesized and preclinically evaluated for PET imaging. One PET ligand, [C-11]31, showed moderate specific binding to the GluN2B subtype.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Multidisciplinary Sciences
Kuan Hu, Lin Xie, Yiding Zhang, Masayuki Hanyu, Zhimin Yang, Kotaro Nagatsu, Hisashi Suzuki, Jiang Ouyang, Xiaoyuan Ji, Junjie Wei, Hao Xu, Omid C. Farokhzad, Steven H. Liang, Lu Wang, Wei Tao, Ming-Rong Zhang
NATURE COMMUNICATIONS
(2020)
Article
Chemistry, Medicinal
Tomoteru Yamasaki, Xiaofei Zhang, Katsushi Kumata, Yiding Zhang, Xiaoyun Deng, Masayuki Fujinaga, Zhen Chen, Wakana Mori, Kuan Hu, Hidekatsu Wakizaka, Akiko Hatori, Lin Xie, Masanao Ogawa, Nobuki Nengaki, Richard Van, Yihan Shao, Douglas J. Sheffler, Nicholas D. P. Cosford, Steven H. Liang, Ming-Rong Zhang
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Article
Medicine, General & Internal
Dan Wu, Yuzhou Lei, Qin Liu, Hua Hu, Huanhuan Li, Lin Xie, Jianbin Zhou
Summary: The study revealed that the expression profile of the CADM1/HER2/STAT3 axis was closely associated with histologic type, stage, and lymph node metastasis in patients with SOT. These molecular data may provide new insights into SOT carcinogenesis and aid in the diagnosis and treatment of patients with SOT.
Article
Biochemical Research Methods
Xiumin Shi, Qing Li, Lulu Zhang, Masayuki Hanyu, Lin Xie, Kuan Hu, Kotaro Nagatsu, Chuan Zhang, Zhengcan Wu, Feng Wang, Ming-Rong Zhang, Kai Yang, Ran Zhu
Summary: The study developed a novel semiconducting polymer nanoparticle-based radiopharmaceutical for targeted radionuclide therapy against GIPR-positive cancers, showing high therapeutic efficiency and biological safety in cell and mouse models.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Oncology
Lin Xie, Kuan Hu, Yanhong Duo, Takashi Shimokawa, Katsushi Kumata, Yiding Zhang, Cuiping Jiang, Lulu Zhang, Nobuki Nengaki, Hidekatsu Wakizaka, Yihai Cao, Ming-Rong Zhang
Summary: The study used a small-molecule radiotracer, C-11-l-1MTrp, to quantitatively and longitudinally visualize whole-body IDO1 dynamics, accurately delineating changes in the cancer-immune milieu and assessing the efficacy of multiple combinatorial immunotherapies. The results suggest that PET imaging of IDO1 with C-11-l-1MTrp can serve as a robust method for tracking IDO1 in therapeutic interventions, highlighting its potential as a new biomarker for personalized cancer immunotherapy strategies.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Pharmacology & Pharmacy
Kuan Hu, Wenyu Wu, Lin Xie, Hao Geng, Yiding Zhang, Masayuki Hanyu, Lulu Zhang, Yinghuan Liu, Kotaro Nagatsu, Hisashi Suzuki, Jialin Guo, Yundong Wu, Zigang Li, Feng Wang, Mingrong Zhang
Summary: The study tracked the movement of a D-dodecapeptide antagonist in vivo using mouse models and found that D-peptides were primarily eliminated by the kidneys and accumulated in tumors, with a single dose effectively delaying tumor growth and improving mouse survival.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Chemistry, Medicinal
Jian Rong, Wakana Mori, Xiaotian Xia, Michael A. Schafroth, Chunyu Zhao, Richard S. Van, Tomoteru Yamasaki, Jiahui Chen, Zhiwei Xiao, Ahmed Haider, Daisuke Ogasawara, Atsuto Hiraishi, Tuo Shao, Yiding Zhang, Zhen Chen, Fuwen Pang, Kuan Hu, Lin Xie, Masayuki Fujinaga, Katsushi Kumata, Yuancheng Gou, Yang Fang, Shuyin Gu, Huiyi Wei, Liang Bao, Hao Xu, Thomas L. Collier, Yihan Shao, Richard E. Carson, Benjamin F. Cravatt, Lu Wang, Ming-Rong Zhang, Steven H. Liang
Summary: Monoacylglycerol lipase (MAGL) is responsible for hydrolyzing 2-arachidonoylglycerol into arachidonic acid in the central nervous system, making it a potential target for treating psychiatric disorders and neurodegenerative diseases. Reversible MAGL inhibitors were designed and synthesized, with compounds 10 and 15 identified as the best performers. Radiolabeling with fluorine-18 and evaluation in rodents and nonhuman primates showed that compound [F-18]15 demonstrated the best performance as a PET radioligand for visualizing MAGL in the brain.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Kuan Hu, Xiaohui Ma, Lin Xie, Yiding Zhang, Masayuki Hanyu, Honoka Obata, Lulu Zhang, Kotaro Nagatsu, Hisashi Suzuki, Rui Shi, Weizhi Wang, Ming-Rong Zhang
Summary: The development of a novel PET tracer [Cu-64]CM-2 for mapping CD133 protein in various cancers demonstrates specific binding to CD133-positive CSCs in preclinical tumor models, making it a state-of-the-art tool for tracking CD133 dynamics and CSCs in refractory cancers.
Article
Chemistry, Multidisciplinary
Ran Cheng, Masayuki Fujinaga, Jing Yang, Jian Rong, Ahmed Haider, Daisuke Ogasawara, Richard S. Van, Tuo Shao, Zhen Chen, Xiaofei Zhang, Erick R. Calderon Leon, Yiding Zhang, Wakana Mori, Katsushi Kumata, Tomoteru Yamasaki, Lin Xie, Shaofa Sun, Lu Wang, Chongzhao Ran, Yihan Shao, Benjamin Cravatt, Lee Josephson, Ming-Rong Zhang, Steven H. Liang
Summary: MAGL is a key enzyme involved in regulating endocannabinoid balance by degrading 2-AG, and selective inhibition of it may have therapeutic implications for various pathologies. A reversible and peripheral-specific radiofluorinated MAGL PET ligand has been developed, showing exceptional specificity and selectivity in BAT, providing a non-invasive imaging tool for studying the role of BAT in ECS-related pathologies.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Engineering, Biomedical
Zeyu Xiao, Duo Wang, Chan Wang, Zerong Chen, Cuiqing Huang, Yuan Yang, Lin Xie, Lulu Zhang, Lingling Xu, Ming-Rong Zhang, Kuan Hu, Zhou Li, Liangping Luo
Summary: Intratumoral immunotherapeutic hydrogel administration is effective in inducing a durable antitumor immune response. A ternary hydrogel composed of PVA, PEI, and magnesium ions has been developed to reverse the immunologically cold phenotype of breast tumors to a hot phenotype by upregulating PD-L1 expression and promoting M1-like macrophage polarization. PEI hydrogel encapsulating an ICB inhibitor exhibits synergistic effects in eliminating tumors and preventing relapse after surgical resection.
MATERIALS TODAY BIO
(2022)
Article
Chemistry, Medicinal
Qingzhen Yu, Katsushi Kumata, Jian Rong, Zhen Chen, Tomoteru Yamasaki, Jiahui Chen, Zhiwei Xiao, Hideki Ishii, Atsuto Hiraishi, Tuo Shao, Yiding Zhang, Kuan Hu, Lin Xie, Masayuki Fujinaga, Chunyu Zhao, Wakana Mori, Thomas Collier, Ahmed Haider, Susumu Tomita, Ming-Rong Zhang, Steven Liang
Summary: TARP gamma-8 is an auxiliary subunit of AMPA receptors that regulates various brain functions. Researchers have developed two novel C-11-labeled probes, one of which showed reasonable brain uptake and specific binding to TARP gamma-8 in both in vitro and in vivo experiments, making it a potential positron-emission tomography ligand for non-invasive quantification of TARP gamma-8 in the mammalian brain.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Lin Xie, Lulu Zhang, Kuan Hu, Masayuki Hanyu, Yiding Zhang, Masayuki Fujinaga, Katsuyuki Minegishi, Takayuki Ohkubo, Kotaro Nagatsu, Cuiping Jiang, Takashi Shimokawa, Kazuma Ashisuke, Noriyuki Okonogi, Shigeru Yamada, Feng Wang, Rui Wang, Ming-Rong Zhang
Summary: The study introduces a targeted radio-pharmaceutical therapy strategy using a small-molecule alpha-emitting radiopharmaceutical, 211At-AITM, to antagonistically recognize and eradicate mGluR1+ human tumors. The therapy shows long-lasting antitumor efficacy with little toxicity across seven subtypes of four common tumors. Mechanistically, 211At-AITM downregulates mGluR1 oncoprotein and induces senescence of tumor cells with a reprogrammed senescence-associated secretory phenotype.
CELL REPORTS MEDICINE
(2023)
Article
Chemistry, Medicinal
Yiding Zhang, Katsushi Kumata, Lin Xie, Yusuke Kurihara, Masanao Ogawa, Tomomi Kokufuta, Nobuki Nengaki, Ming-Rong Zhang
Summary: In this study, [C-11-carbonyl]BPTES ([C-11]BPTES) was synthesized as a positron emission tomography (PET) probe for the first time and its biodistribution in mice was assessed using PET. The results showed high uptake levels of [C-11]BPTES in the liver, kidney, and small intestine of mice.
Article
Chemistry, Organic
Faiza Diaba, Gisela Trenchs
Summary: The first violet light-mediated synthesis of gamma- and delta-lactams from N-alkenyl trichloroacetamides is reported in this paper. The reactions are conducted in tetrahydrofuran or 2-methyltetrahydrofuran as the sole solvent without catalysts or additives, under non-anhydrous conditions in an air atmosphere where the solvent serves as the radical initiator.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Feroze Hussain, Sajjad Ahmed, Ashiq Hussain Padder, Qazi Naveed Ahmed
Summary: This study reports a novel and efficient one-pot synthesis method for mixed phosphorotrithioates, which does not require supplementary additives and shows broad applicability.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Hyunjin Oh, Ikyon Kim
Summary: A new 1,2,4-triazole-pyrrolo[1,2-a]pyrazine hybrid system, 6-acylpyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazine, was synthesized using a catalyst-free method. This method involved sequential exposure of pyrrole-2-carbonitrile-derived substrates to DMF-DMA and acyl hydrazide, resulting in the formation of acylated pyrazine and 1,2,4-triazole rings, enabling the installation of various substituents at specific positions on the core skeleton.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Ming Yan, Si-fan Wang, Yong-po Zhang, Jin-zhong Zhao, Zhuo Tang, Guang-xun Li
Summary: Here we developed an efficient photocatalytic approach for the convenient preparation of sulfinamides. The reaction allows for the gram-scale preparation of sulfinamides and the one-pot synthesis of various sulfonyl amides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Farzaneh Bandehali-Naeini, Zahra Tanbakouchian, Noushin Farajinia-Lehi, Nicolas Mayer, Morteza Shiri, Martin Breugst
Summary: Two tandem catalytic systems were developed for the synthesis of novel 3,4-disubstituted maleimides using the same Ugi adducts. Different maleimide structures can be synthesized using either Pd or Cu catalysis.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Article
Chemistry, Organic
Tanya Raghava, Anjan Chattopadhyay, Subhadeep Banerjee, Nivedita Sarkar
Summary: Amine substitution of two ortho fluorine atoms of tetrafluoroterephthalonitrile through SNAr chemistry is easily achievable. But further fluorine substitution is only possible under forcing conditions, yielding valuable fluorophores for bioimaging.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
Review
Chemistry, Organic
Anju Chadha, Santosh Kumar Padhi, Selvaraj Stella, Sowmyalakshmi Venkataraman, Thangavelu Saravanan
Summary: Alcohol dehydrogenases are enzymes that use cofactors for oxidation or reduction reactions of alcohols or carbonyl compounds. They are utilized in green chemistry and have applications in the production of pharmaceuticals. Recombinant enzymes have solved the challenge of producing purified enzymes in large quantities. Engineered alcohol dehydrogenases have been used in asymmetric synthesis in industry. Various methods have been established for regenerating expensive cofactors to make the enzymatic process more efficient and economically viable.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2024)
