Review
Pharmacology & Pharmacy
Truong Giang Luu, Hee-Kwon Kim
Summary: TSPO plays important roles in cellular functions and its abnormal expression is associated with pathological disorders, making it a biomarker for related diseases. PET, as a non-invasive imaging technique, can detect diseases related to TSPO expression. Recent studies have focused on the development of F-18-labeled TSPO as PET tracers.
Article
Radiology, Nuclear Medicine & Medical Imaging
Gjertrud L. Laurell, Pontus Plaven-Sigray, Aurelija Jucaite, Andrea Varrone, Kelly P. Cosgrove, Claus Svarer, Gitte M. Knudsen, R. Todd Ogden, Francesca Zanderigo, Simon Cervenka, Ansel T. Hillmer, Martin Schain
Summary: The study utilized a novel method SIME to estimate V-ND, demonstrating significantly lower V-ND in patients with alcohol use disorder and Parkinson's disease compared to controls. The findings suggest that differences in nondisplaceable binding may exist between different patient groups and conditions in TSPO PET studies.
JOURNAL OF NUCLEAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Nakul R. Raval, Gustavo Angarita, David Matuskey, Rachel Miller, Lindsey R. Drake, Michael Kapinos, Nabeel Nabulsi, Yiyun Huang, Richard E. Carson, Stephanie S. O'Malley, Kelly P. Cosgrove, Ansel T. Hillmer
Summary: The negative effects of alcohol on the immune system in both the periphery and the brain are not fully understood. This study used positron emission tomography to measure the immune response to alcohol in the brain, and found that alcohol significantly increased immune markers in the brain and affected plasma cytokines.
MOLECULAR PSYCHIATRY
(2023)
Article
Clinical Neurology
Sini Toppala, Laura L. Ekblad, Jouni Tuisku, Semi Helin, Jarkko J. Johansson, Hanna Laine, Eliisa Loyttyniemi, Paivi Marjamaki, Kaj Blennow, Henrik Zetterberg, Antti Jula, Matti Viitanen, Juha O. Rinne
Summary: While there was no association between amyloid and neuroinflammation in the overall study group, neuroinflammation was associated with amyloid among the subgroup at early stages of amyloid pathology. Higher body mass index, HOMA-IR, and hs-CRP were associated with higher neuroinflammation in brain regions where A beta accumulation is first detected in Alzheimer disease.
Review
Radiology, Nuclear Medicine & Medical Imaging
Viviane Bouilleret, Stefanie Dedeurwaerdere
Summary: This review discusses the potential of using TSPO PET imaging to provide insights for epilepsy clinic and future treatments targeting neuroinflammatory processes. Despite evidence from preclinical studies showing a correlation between TSPO levels and epilepsy-related factors, TSPO PET imaging has not been widely adopted in clinical settings. Further research is needed to explore the value of TSPO PET in optimizing surgical assessment and supporting the development of anti-inflammatory treatments for epilepsy.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(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
Clinical Neurology
Boris-Stephan Rauchmann, Matthias Brendel, Nicolai Franzmeier, Lena Trappmann, Mirlind Zaganjori, Ersin Ersoezlue, Estrella Morenas-Rodriguez, Selim Guersel, Lena Burow, Carolin Kurz, Jan Haeckert, Maia Tato, Julia Utecht, Boris Papazov, Oliver Pogarell, Daniel Janowitz, Katharina Buerger, Michael Ewers, Carla Palleis, Endy Weidinger, Gloria Biechele, Sebastian Schuster, Anika Finze, Florian Eckenweber, Rainer Rupprecht, Axel Rominger, Oliver Goldhardt, Timo Grimmer, Daniel Keeser, Sophia Stoecklein, Olaf Dietrich, Peter Bartenstein, Johannes Levin, Gunter Hoglinger, Robert Perneczky
Summary: This study found that microglial activation patterns are associated with highly connected brain regions in early Alzheimer's disease (AD) patients. Functional connectivity showed a stronger association with microglial activation compared to MRI structural connectivity. AD patients exhibited increased uptake of the TSPO-PET tracer in the bilateral anterior medial temporal lobe, and higher tracer uptake was associated with cognitive impairment and dementia severity.
ANNALS OF NEUROLOGY
(2022)
Article
Chemistry, Analytical
Dai Shi, Zhan Si, Zhan Xu, Yuan Cheng, Qingyu Lin, Zhequan Fu, Wenhui Fu, Tingting Yang, Hongcheng Shi, Dengfeng Cheng
Summary: This study confirmed the high expression of TREM2 in tumors and successfully synthesized the radioligand Ga-68-NOTA-COG1410 targeting TREM2. The radioligand showed high uptake in tumors and not in areas of inflammation, making it useful for distinguishing tumors from inflammation. The use of Ga-68-NOTA-COG1410 may enhance the effectiveness of PET imaging of digestive system tumors.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Krishna Kanta Ghosh, Parasuraman Padmanabhan, Chang-Tong Yang, Zhimin Wang, Mathangi Palanivel, Kian Chye Ng, Jia Lu, Jan Carlstedt-Duke, Christer Halldin, Balazs Gulyas
Summary: This study investigates the use of PET imaging with two radioligands, [C-11]PBR28 and [F-18]flumazenil, in a rodent TBI model to accurately quantify molecular-cellular changes. The results show the potential of these radioligands in exploring neuroinflammation and cell activity in the brain, and their possible application in studying nanoparticle delivery mechanisms in TBI treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Carla Bianca Luena Victorio, Rasha Msallam, Wisna Novera, Joanne Ong, Tham Jing Yang, Arun Ganasarajah, Jenny Low, Satoru Watanabe, Ann-Marie Chacko
Summary: This study investigates the changes in TSPO expression in the adult brain associated with Zika virus infection. It found that TSPO expression increased with disease severity, driven by TSPO-positive microglia, infiltrating monocytes, and TSPO-expressing immune cells. TSPO radioligands showed effectiveness in detecting TSPO expression in infected brains. [F-18]FEPPA-PET imaging correlated with disease severity and neuroinflammation, but also showed significant blood pool activity due to TSPO expression by immune cells.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Cell Biology
Calina Betlazar, Ryan J. Middleton, Nicholas Howell, Ben Storer, Emma Davis, Justin Davies, Richard Banati, Guo-Jun Liu
Summary: The study found that both low and high doses of ionizing radiation reduced TSPO expression in the brain's vascular compartment without inducing TSPO expression in parenchymal microglia.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Sang Hee Lee, Nunzio Denora, Valentino Laquintana, Giuseppe Felice Mangiatordi, Angela Lopedota, Antonio Lopalco, Annalisa Cutrignelli, Massimo Franco, Pietro Delre, In Ho Song, Hye Won Kim, Su Bin Kim, Hyun Soo Park, Kyungmin Kim, Seok-Yong Lee, Hyewon Youn, Byung Chul Lee, Sang Eun Kim
Summary: The new TSPO ligand [F-18]BS224 demonstrated high affinity and selectivity, allowing it to identify abnormal TSPO expression in neuroinflammation independent of the rs6971 polymorphism, indicating potential clinical utility.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Article
Chemistry, Multidisciplinary
Neelam Kumari, Priya Singh, Deepika Singh, Akanksha Mishra, Ankur Kaul, Himanshu Ojha, Anjani Kumar Tiwari
Summary: This study evaluated the use of PIC and EDTA-based acetamidobenzoxazolone probes as diagnostic agents for TSPO. In silico analysis was used to assess the binding efficacy of these probes towards TSPO, and in vivo experiments were conducted using a mouse model to observe their absorption and distribution in different organs. Additionally, spectroscopic analysis with BSA was performed to better understand the nature of these probes as diagnostic agents.
NEW JOURNAL OF CHEMISTRY
(2023)
Review
Immunology
Rong Zhou, Bin Ji, Yanyan Kong, Limei Qin, Wuwei Ren, Yihui Guan, Ruiqing Ni
Summary: Neuroinflammation plays a significant role in the pathogenesis of Alzheimer's disease, and molecular imaging techniques have provided valuable insights into its involvement in disease progression. The development of new generation translocator protein tracers and other imaging technologies offers promise for monitoring disease progression and identifying potential targets for future research.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Radiology, Nuclear Medicine & Medical Imaging
Fabien Chauveau, Guillaume Becker, Herve Boutin
Summary: This study systematically reviewed TSPO radiotracers, finding that challengers have better signal-to-noise ratio in neuroinflammatory diseases, but genetic stratification could hinder their clinical implementation. New challengers insensitive to TSPO human polymorphism are under evaluation.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2021)
Review
Chemistry, Medicinal
Federica Sommonte, Ilaria Arduino, Giuseppe Francesco Racaniello, Antonio Lopalco, Angela Assunta Lopedota, Nunzio Denora
Summary: Lipid-based formulations, such as Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs), are promising strategies for non-invasive specific treatment of CNS-related diseases by overcoming the limitations posed by the Blood-Brain Barrier. The concept of age-related targeting could be a successful choice in tailoring treatments to different needs and characteristics based on disease and age of onset.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Physical
Rosa Maria Iacobazzi, Fabio Vischio, Ilaria Arduino, Fabio Canepa, Valentino Laquintana, Maria Notarnicola, Maria Principia Scavo, Giusy Bianco, Elisabetta Fanizza, Angela Assunta Lopedota, Annalisa Cutrignelli, Antonio Lopalco, Amalia Azzariti, Maria Lucia Curri, Massimo Franco, Gianluigi Giannelli, Byung Chul Lee, Nicoletta Depalo, Nunzio Denora
Summary: In this study, solid lipid nanoparticles (SLNs) co-encapsulating superparamagnetic iron oxide nanoparticles and sorafenib were used for magnetic-guided drug delivery to the liver. Experimental and simulation analyses showed the impact of magnetic field topology on SLNP accumulation in liver tissues, with the magnet configuration resulting in higher magnetic targeting efficiency determined by evaluating iron content in liver tissues. These findings demonstrated the potential of using magnetic configurations to enhance drug delivery efficiency to specific target tissues such as the liver.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Oncology
Rosa Maria Iacobazzi, Ilaria Arduino, Roberta Di Fonte, Angela Assunta Lopedota, Simona Serrati, Giuseppe Racaniello, Viviana Bruno, Valentino Laquintana, Byung-Chul Lee, Nicola Silvestris, Francesco Leonetti, Nunzio Denora, Letizia Porcelli, Amalia Azzariti
Summary: This research presents a new potential therapeutic approach for pancreatic ductal adenocarcinoma by developing a double actively targeted gemcitabine delivery system. The study demonstrates that the pH-responsive and uPAR-targeted polymeric micelles can enhance the antitumor properties of gemcitabine and potentially overcome drug resistance in pancreatic cancer.
Article
Pharmacology & Pharmacy
Monica Pistone, Giuseppe Francesco Racaniello, Rosanna Rizzi, Rosa Maria Iacobazzi, Ilaria Arduino, Antonio Lopalco, Angela Assunta Lopedota, Nunzio Denora
Summary: The study aimed to create a solid oral formulation of budesonide (BD) loaded with direct powder extrusion (DPE) 3D printing and fluid bed coating techniques for the treatment of eosinophilic colitis (EC) in paediatric patients. BD, the preferred medication for EC treatment, has poor water solubility and low absorption. The DPE 3D approach was used to create Mini-Tablets (MTs) suitable for paediatric patients, and the inclusion of hydroxypropyl-beta-cyclodextrin improved the solubility and dissolution rate of BD. The MTs were coated with an enteric polymer to achieve site-specific drug release at the intestinal level.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Federica Sommonte, Ilaria Arduino, Rosa Maria Iacobazzi, Mattia Tiboni, Federico Catalano, Roberto Marotta, Martina Di Francesco, Luca Casettari, Paolo Decuzzi, Angela Assunta Lopedota, Nunzio Denora
Summary: After 20 years of research, nanoscale delivery systems for biologicals in nanomedicine have become clinically relevant. Microfluidic-based production of solid lipid nanoparticles (SLNs) is shown to be efficient in encapsulating and delivering lysozyme (LZ), with smaller size and higher encapsulation efficacy compared to conventional methods. This study demonstrates the potential of microfluidic production of SLNs for encapsulation and delivery of complex biological molecules.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Review
Chemistry, Medicinal
Federica Sommonte, Nunzio Denora, Dimitrios A. Lamprou
Summary: Nanomedicine has developed rapidly in recent years for finding new therapies to treat challenging diseases. Microfluidic technology (MF) and additive manufacturing (AM) have gained popularity in the life science field, offering various benefits and drawbacks. By optimizing operational parameters, MF and AM can overcome existing limitations and their combination can provide highly-customizable and cost-effective solutions. This collaboration between MF and AM shows promising potential for impactful innovation in the near future.
Article
Chemistry, Medicinal
Pasquale Linciano, Claudia Sorbi, Giacomo Rossino, Daniela Rossi, Andrea Marsala, Nunzio Denora, Martina Bedeschi, Noemi Marino, Giacomo Miserocchi, Giulio Dondio, Marco Peviani, Anna Tesei, Simona Collina, Silvia Franchini
Summary: In this study, novel benzylpiperidine/benzylpiperazine-based compounds were designed and tested as Sigma-1 receptor (S1R) agonists. The compounds 6b and 8b showed high affinity for S1R and selectivity over S2R and NMDAR. They exhibited neuroprotective activity and enhanced neurite outgrowth in cell lines, as well as good efficacy/safety profile in in-vitro and in-vivo models. These results encourage further preclinical investigations of compounds 6b and 8b on neurodegenerative diseases.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Bashar M. Thejer, Vittoria Infantino, Anna Santarsiero, Ilaria Pappalardo, Francesca S. Abatematteo, Sarah Teakel, Ashleigh Van Oosterum, Robert H. Mach, Nunzio Denora, Byung Chul Lee, Nicoletta Resta, Rosanna Bagnulo, Mauro Niso, Marialessandra Contino, Bianca Montsch, Petra Heffeter, Carmen Abate, Michael A. Cahill
Summary: Sigma-2 receptor (S2R) is functionally associated with both transmembrane protein TMEM97 and translocator protein (TSPO). This study provides evidence of the interaction between S2R and TSPO, as well as the physical colocalization of TMEM97 and TSPO in certain cancer cells. Additionally, the role of S2R-interacting partner PGRMC1 was clarified. This is the first suggestion of a functional interaction between TSPO and TMEM97, which can be influenced by S2R ligands.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Patrick Knoll, Giuseppe Francesco Racaniello, Valentino Laquintana, Florina Veider, Ahmad Saleh, Anna Seybold, Nunzio Denora, Andreas Bernkop-Schnuerch
Summary: The aim of this study was to evaluate the uptake mechanism of thiolated nanostructured lipid carriers (NLCs). NLCs with different modifications were evaluated for size, surface morphology, stability, cytotoxicity, adhesion to the cell surface, internalization, and their influence on paracellular permeability. The results showed that NLCs with shorter PEG chains and thiolation exhibited higher cellular uptake. The cellular uptake of all NLCs was mainly clathrin-mediated endocytosis, and thiolated NLCs also showed caveolae-dependent and clathrin-and caveolae-independent uptake.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Review
Pharmacology & Pharmacy
Aida Loshaj Shala, Ilaria Arduino, Mimoza Basholli Salihu, Nunzio Denora
Summary: The development of efficient treatments for tumors affecting the central nervous system (CNS) remains an open challenge. Gliomas are particularly difficult to treat, causing death in adult patients just over 6 months after diagnosis without treatment. Quercetin, derived from fruits and vegetables, has shown promising potential in reducing the progression of tumor cells through multiple molecular mechanisms. Further research in the field of pediatric oncology may offer new perspectives on brain cancer treatment for children.
Article
Pharmacology & Pharmacy
Paolo Bongiorno, Antonio Lopalco, Antonella Casiraghi, Antonio Spennacchio, Alessandro Pitruzzella, Angela Assunta Lopedota, Paola Minghetti, Nunzio Denora
Summary: This study aimed to develop a controlled one-step process for cannabis olive oil preparations using digital technologies. The TGE and TGE-PE methods were found to be effective in quantitatively extracting cannabinoids and increasing the concentrations of terpenes in the oil extracts.
Article
Chemistry, Medicinal
Jaekyung Park, Sobia Wasim, Jae Ho Jung, Mi-hyun Kim, Byung Chul Lee, Mohammad Maqusood Alam, Sang-Yoon Lee
Summary: The translocator protein (TSPO) is a biological target associated with microglial activation in CNS diseases. A novel TSPO ligand, GMA 15, was discovered with enhanced affinity compared to the reference standard. Further optimization is needed for potential therapeutic applications.
Article
Cell Biology
Seung Woo Choi, Hye Kyoung Hong, Jehwi Jeon, Ji Young Choi, Minah Kim, Pilhan Kim, Byung Chul Lee, Se Joon Woo
Summary: The development of choroidal neovascularization (CNV) is crucial in the pathophysiology and prognosis of exudative age-related macular degeneration (AMD). Current imaging techniques have limitations in accurately visualizing CNV lesions and expressing CNV activity. Using the FITC-labeled RGD peptide, which has an affinity for integrin α(v)β(3) expressed in neovascular endothelial cells, improved visualization and precise localization of CNV lesions were achieved. This novel dye, FITC-RGD(2), shows promise in the early detection and treatment of neovascular retinal diseases, including AMD.
Review
Pharmacology & Pharmacy
Dafina Fondaj, Ilaria Arduino, Angela Assunta Lopedota, Nunzio Denora, Rosa Maria Iacobazzi
Summary: Nanomedicines have made significant advances in recent years, providing improved drug solubility, stability, precise delivery, and targeted therapy. Biomimetic nanoparticles have been developed as novel drug carriers, with microfluidic production technique emerging as a promising approach. Leveraging microfluidics and biomimetic nanoparticles can lead to advancements in personalized medicine.
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)
