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J Control Release ; 281: 178-188, 2018 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-29777796

RESUMEN

The sodium pump Na+/K+ ATPase a1 subunit(NKA a1), an attractive cancer-related biomarker and therapeutic target, is closely related to the development and progression of several cancers including breast cancer. Currently, a NKA a1 inhibitor, UNBS1450, has already evidenced its great therapeutic potential in personalized cancer treatment. The ability of non-invasive imaging of NKA a1 expression would be useful for selecting cancer patients who may benefit from this drug. Here, we identified an S3 peptide that is specifically homed to breast cancer by phage display. All data of in vitro and in vivo experiments suggested the excellent targeting character of the S3 peptide. As the binding activity of the S3 phage was positively correlated to the level of NKA α1 expression in various breast cancer cells, NKA α1 was validated as the primary target of the S3 peptide. Based on immunohistochemistry staining result of 107 breast cancer patients, NKA α1 was verified to be a novel tracking marker and a prognostic predictor for breast cancer. Importantly, we proposed and validated an S3 peptide-based radiotracer 18F-ALF-NOTA-S3 for PET (Positron Emission Tomography) imaging of breast cancer and other NKA α1-overexpressing cancers, including hepatocellular carcinoma and non-small cell lung cancer, in mouse models. Our findings demonstrated the potential application of 18F-ALF-NOTA-S3 for visualization of NKA α1-positive lesions, which provide a new approach to character tumor phenotypic imaging.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Péptidos/metabolismo , Radiofármacos/química , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/metabolismo , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Línea Celular Tumoral , Femenino , Radioisótopos de Flúor , Xenoinjertos , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Pulmonares/diagnóstico por imagen , Ratones Endogámicos C57BL , Imagen Óptica/métodos , Tomografía de Emisión de Positrones/métodos , Subunidades de Proteína/metabolismo
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