A benzenesulfonamide derivative as a novel PET radioligand for CXCR4.
Bioorg Med Chem
; 28(2): 115240, 2020 01 15.
Article
em En
| MEDLINE
| ID: mdl-31843463
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Carcinoma de Células Escamosas
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Compostos Radiofarmacêuticos
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Receptores CXCR4
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Tomografia por Emissão de Pósitrons
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Neoplasias de Cabeça e Pescoço
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article