Article
Medicine, General & Internal
Mohammed Al-Zubaidi, Pravin Viswambaram, Steve McCombie, Elizabeth Liow, Nat Lenzo, Tom Ferguson, Andrew D. Redfern, Richard Gauci, Dickon Hayne
Summary: Bladder cancer is a lethal disease with limited conventional imaging modalities for accurate staging. This study aims to investigate the use of (89)Zirconium-labelled girentuximab PET in the staging of bladder and urothelial carcinomas.
Review
Biochemistry & Molecular Biology
Kuo-Ting Chen, Yann Seimbille
Summary: Carbonic anhydrase IX (CAIX) is a tumor-specific and hypoxia-induced biomarker that can be used for molecular imaging of solid malignancies. Nuclear imaging and optical fluorescence imaging are powerful tools for the diagnosis and treatment of tumors, and many CAIX-targeted molecular imaging probes have been developed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Daan F. Boreel, Paul N. Span, Annemarie Kip, Milou Boswinkel, Johannes P. W. Peters, Gosse J. Adema, Johan Bussink, Sandra Heskamp
Summary: Limited oxygen diffusion and increased oxygen consumption in solid malignancies lead to chronic hypoxia, which induces radioresistance and an immunosuppressive microenvironment. This study aimed to develop a radiolabeled antibody to visualize chronic hypoxia and study immune cell populations in these hypoxic areas. The results showed that the radiotracer binds to CAIX-expressing cells in vitro and accumulates in CAIX+ areas in vivo. The technique can quantitatively distinguish between tumor models with varying CAIX+ fractions and identified less infiltration of immune cells in the CAIX+ areas.
MOLECULAR PHARMACEUTICS
(2023)
Article
Medicine, Research & Experimental
Sanne A. M. van Lith, Fokko J. Huizing, Gerben M. Franssen, Bianca A. W. Hoeben, Jasper Lok, Sofia Doulkeridou, Otto C. Boerman, Martin Gotthardt, Paul M. P. van Bergen en Henegouwen, Johan Bussink, Sandra Heskamp
Summary: This study compared variants of CAIX-binding VHH B9 with different affinities (low and high) for SPECT imaging of CAIX expression. The results showed that B9 variants with ABD demonstrated better tumor uptake, but some uptake was CAIX-independent, limiting their use in hypoxia assessment.
MOLECULAR PHARMACEUTICS
(2022)
Article
Chemistry, Medicinal
Ozlem Akgul, Srishti Singh, Jacob T. Andring, Robert McKenna, Silvia Selleri, Fabrizio Carta, Andrea Angeli, Claudiu T. Supuran
Summary: A series of taurine substituted sulfonamide derivatives with ureido moiety at the tail section were synthesized as selective inhibitors of tumor associated human Carbonic Anhydrase (CA) IX and XII. These derivatives showed a strong dependence on the presence of ureido moiety and demonstrated highly stabilized ligand-protein complex with specific amino acid residues in both hCA II and hCA IX-mimic.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Miriam Zatovicova, Ivana Kajanova, Monika Barathova, Martina Takacova, Martina Labudova, Lucia Csaderova, Lenka Jelenska, Eliska Svastova, Silvia Pastorekova, Adrian L. Harris, Jaromir Pastorek
Summary: Hypoxia in the tumor microenvironment is a major factor in cancer progression, and low levels of oxygen may indicate treatment failure. Carbonic anhydrase IX (CA IX) is a precise target in hypoxic tumors, and its presence contributes to the failure of standard therapy. Humanized antibodies against CA IX show promise as suitable therapies for hypoxic tumors, with the ability to modulate the tumor microenvironment, induce an immune response, and block metastasis formation.
CANCER & METABOLISM
(2022)
Article
Chemistry, Analytical
Zhuang Hu, Ruihan Li, Xinyue Cui, Changjun Hu, Zilin Chen
Summary: Osteosarcoma (OS) is a common and deadly carcinoma of the skeletal system. Detecting the tumor early and implementing effective interventional therapies can improve limb salvage and overall survival rates. Carbonic anhydrase IX (CA IX) is an important functional protein in tumor acidification and is considered a potential biomarker. This study developed a pH-sensitive near-infrared imaging probe called ABSi-783 by combining the CA IX inhibitor ABSi with IR783. The probe has high selectivity for osteosarcoma imaging, can detect pH changes in vitro, and has demonstrated potential for targeted diagnosis and surgical treatment monitoring of osteosarcoma.
SENSORS AND ACTUATORS B-CHEMICAL
(2023)
Article
Biochemistry & Molecular Biology
Utpal K. Mondal, Kate Doroba, Ahmed M. Shabana, Rachel Adelberg, Md. Raqibul Alam, Claudiu T. Supuran, Marc A. Ilies
Summary: The study identified a series of PEGylated CA inhibitors that effectively suppressed the growth and proliferation of tumor cells by attaching to different lengths of PEG backbones. In experimental models, PEGylated CA inhibitors with short to medium PEG backbones were found to have higher anticancer effects under both normoxic and hypoxic conditions, as well as in tumor spheroid models. The findings confirmed that PEGylated CA inhibitors did not affect the cell viability of CA IX-negative NCI-H23 tumor spheroids, indicating a potential CA IX-mediated cell killing for these anticancer agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Ji Hyeon Kim, Peter Verwilst, Miae Won, Junhyoung Lee, Jonathan L. Sessler, Jiyou Han, Jong Seung Kim
Summary: Breast cancer stem cells (BCSCs) are a major contributor to the unfavorable outcomes seen in many breast cancer patients, as they are more prevalent in hypoxic environments and refractory to traditional chemotherapy. A small molecule construct named AzCDF has been developed to target BCSCs effectively in the hypoxic tumor environment, reducing tumor growth and migration. This is the first time a CSC-targeting small molecule has been shown to prevent tumorigenesis in an animal model.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Sebastian Oehler, Marco Catalano, Ilario Scapozza, Martina Bigatti, Gabriele Bassi, Nicholas Favalli, Michael R. Mortensen, Florent Samain, Jorg Scheuermann, Dario Neri
Summary: The study optimized selection procedures with CAIX-expressing tumor cells as a model system, achieving higher enrichment factors, and found that homobivalent display of acetazolamide can improve ligand recovery and enrichment factors.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Marta Venturella, Alessandro Falsini, Federica Coppola, Gaia Giuntini, Fabio Carraro, Davide Zocco, Antonio Chiesi, Antonella Naldini
Summary: This study investigated the effects of hypoxia on the release of small extracellular vesicles (sEVs) in two melanoma in vitro models. It was found that melanoma cells release sEVs under both normoxic and hypoxic conditions, but only hypoxia-induced sEVs express CA-IX mRNA and protein. An optimized ELISA assay provided evidence for CA-IX protein expression on the membranes of the sEVs. These CA-IX-positive sEVs may serve as potential biomarkers for liquid biopsy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Sridhar Goud Nerella, Priti Singh, Pavitra S. Thacker, Mohammed Arifuddin, Claudiu T. Supuran
Summary: Positron emission tomography (PET) and fluorescent imaging are important in medical diagnosis, oncologic research, and drug development. PET estimates physiological changes at the molecular level using radiotracers, while fluorescent imaging detects molecular level changes using labeled probes. This review focuses on PET radiotracers and fluorescent probes for diagnosing and treating tumors expressing hCA IX and hCA XII.
BIOORGANIC CHEMISTRY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Oana C. Kulterer, Sarah Pfaff, Wolfgang Wadsak, Nathalie Garstka, Mesut Remzi, Chrysoula Vraka, Lukas Nics, Markus Mitterhauser, Franziska Bootz, Samuele Cazzamalli, Nikolaus Krall, Dario Neri, Alexander R. Haug
Summary: Tc-99m-PHC-102 demonstrates good tolerability and targeting performance in patients with ccRCC, with the potential to serve as a companion diagnostic agent for future CAIX-targeting therapeutics.
JOURNAL OF NUCLEAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Ashraf K. El-Damasy, Hyun Ji Kim, Alessio Nocentini, Seon Hee Seo, Wagdy M. Eldehna, Eun-Kyoung Bang, Claudiu T. Supuran, Gyochang Keum
Summary: A series of 6-ureido/amidocoumarins were designed and synthesised to develop potent and isoform-selective carbonic anhydrase inhibitors. The target coumarins effectively inhibited tumour-related isoforms hCA IX and hCA XII, while not inhibiting cytosolic off-target isoforms hCA I and II. The most promising compound, 3,5-bis-trifluoromethylphenyl ureidocoumarin 5i, showed the best anticancer activity.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Elena Andreucci, Alessio Biagioni, Sara Peri, Giampaolo Versienti, Fabio Cianchi, Fabio Staderini, Lorenzo Antonuzzo, Claudiu T. Supuran, Erika Olivo, Elisa Pasqualini, Luca Messerini, Daniela Massi, Matteo Lulli, Jessica Ruzzolini, Silvia Peppicelli, Francesca Bianchini, Nicola Schiavone, Lido Calorini, Lucia Magnelli, Laura Papucci
Summary: Gastric cancer is a common malignancy with high mortality rates, mainly due to the development of chemoresistance. Carbonic anhydrase IX (CAIX) has been identified as a potential biomarker associated with poor prognosis in various solid cancers. In this study, it was found that non-responder gastric cancer patients and drug-resistant gastric cancer cell lines showed increased expression of CAIX compared to responder patients and control cells, respectively. Furthermore, a drug called SLC0111 was found to improve the therapy response of both wild-type and resistant gastric cancer cells, suggesting its potential in overcoming chemoresistance.