A benzenesulfonamide derivative as a novel PET radioligand for CXCR4 |
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| Affiliation: | 1. Department of Radiation Oncology, Emory University School of Medicine, USA;2. Department of Radiology and Image Sciences, Emory University School of Medicine, USA;3. Winship Cancer Institute, Atlanta, GA 30322, USA;1. Chemistry Department, Faculty of Science, King Khalid University, Abha 61413, Saudi Arabia;2. Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City 11884, Cairo, Egypt;3. Chemistry Department, Faculty of Science, Jazan University, Jazan, Saudi Arabia;4. Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia;5. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, 11884 Nasr City, Cairo, Egypt;6. Biology and Chemistry Department, Al-Qunfudah University College, Umm Al-Qura University, Al-Qunfudah 1109, Saudi Arabia;7. Pharmaceutical Chemistry Department, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia;8. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, 11884 Nasr City, Cairo, Egypt;9. Chemistry Department, Faculty of Science and Art, Al-Baha University, Al-Baha 1988, Saudi Arabia;10. Pharmacology and Toxicology Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 41477, Saudi Arabia;1. Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai, 201620, China;2. Department Chemistry, Rhodes University, P. O Box, Grahamstown, South Africa;1. Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1–3, Moscow 119991, Russian Federation;2. EDASA Scientific, Via Stingi 37, San Salvo 66050, Italy;3. Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan;4. Dulbecco Telethon Laboratory of Prions & Amyloids, Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, Via Sommarive 9, Trento 38123, Italy;5. A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Vavilov St. 28, Moscow, Russian Federation;1. Laboratório de Bioquímica Microbiana, Departamento de Microbiologia Geral, IMPG, Universidade Federal do Rio de Janeiro, CEP 21949-900 Rio de Janeiro, RJ, Brazil;2. Instituto de Química de São Carlos, Universidade de São Paulo, CP 780, CEP 13560-970 São Carlos, SP, Brazil;3. Departamento de Virologia, IMPG, Universidade Federal do Rio de Janeiro, CEP 21949-900 Rio de Janeiro, RJ, Brazil;1. Dipartimento di Scienze Chimiche e Farmaceutiche, Università Degli Studi di Trieste, Via Licio Giorgeri 1, 34127, Trieste, Italy;2. Molecular Modeling Section (MMS), Dipartimento di Scienze Del Farmaco, Università di Padova, Via Marzolo 5, 35131, Padova, Italy;3. Laboratory of Bioorganic Chemistry, NIDDK, National Institute of Health, Bethesda, MD, USA;1. Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 02447, Republic of Korea;2. Department of Life and Nanopharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea;3. Department of Physiology and Pharmacology, Hotchkiss Brain Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary T2N 4N1, Canada;4. KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Republic of Korea |
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| Abstract: | CXCR4 is involved in various diseases such as inflammation, tumor growth, and cancer metastasis through the interaction with its natural endogenous ligand, chemokine CXCL12. In an effort to develop imaging probes for CXCR4, we developed a novel small molecule CXCR4-targeted PET agent (compound 5) by combining our established benzenesulfonamide scaffold with a labeling component by virtue of click chemistry. 5 shows nanomolar affinity (IC50 = 6.9 nM) against a known CXCR4 antagonist (TN14003) and inhibits more than 65% chemotaxis at 10 nM in vitro assays. Radiofluorinated compound 5 ([18F]5) demonstrates a competitive cellular uptake against CXCL12 in a dose-dependent manner. Further, microPET images of [18F]5 exhibits preferential accumulation of radioactivity in the lesions of λ-carrageenan-induced paw edema, human head and neck cancer orthotopic xenograft, and metastatic lung cancer of each mouse model. |
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| Keywords: | C-X-C chemokine receptor type 4 (CXCR4) CXCL12 Molecular imaging probe Positron emission tomography (PET) Inflammation Head and neck cancer Metastasis GPCRs" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" G-protein-coupled receptors CXCR4" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" C-X-C chemokine receptor type 4 CXCL12" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" C-X-C chemokine ligand 12 SDF-1" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" stromal cell-derived factor-1 HIV" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" human immunodeficiency virus SCCHN" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" squamous cell carcinoma of head and neck PDB" },{" #name" :" keyword" ," $" :{" id" :" k0105" }," $$" :[{" #name" :" text" ," _" :" protein databank EC" },{" #name" :" keyword" ," $" :{" id" :" k0115" }," $$" :[{" #name" :" text" ," _" :" effective concentration DTPA" },{" #name" :" keyword" ," $" :{" id" :" k0125" }," $$" :[{" #name" :" text" ," _" :" diethylenetriamine pentaacetate DOTA" },{" #name" :" keyword" ," $" :{" id" :" k0135" }," $$" :[{" #name" :" text" ," _" :" dodecane tetraacetic acid NOTA" },{" #name" :" keyword" ," $" :{" id" :" k0145" }," $$" :[{" #name" :" text" ," _" :" triazacyclononane triacetic acid |
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