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1.
Mol Imaging Biol ; 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31792839

RESUMO

PURPOSE: Magnetic resonance imaging (MRI) has a high spatial resolution for detecting hepatocellular carcinoma (HCC). Integrin α6 has emerged as a diagnostic and prognostic biomarker of HCC. Here, we developed the MR contrast agent RWY-dL-(Gd-DOTA)4 based on the integrin α6-targeted RWY peptide that we previously identified to detect HCC. PROCEDURES: Contrast-enhanced MRI was carried out to evaluate the use of RWY-dL-(Gd-DOTA)4 to detect HCC lesions in subcutaneous and diethylnitrosamine (DEN)-induced HCC mouse models. RESULTS: Enhancement MR signals were observed in HCC-LM3 subcutaneous liver tumors in the first 5 min post-injection of RWY-dL-(Gd-DOTA)4 at a low dose of 0.03 mmol Gd/kg. Moreover, RWY-dL-(Gd-DOTA)4 generated superior contrast enhancement for liver tumors in chemical-induced HCC mice. Importantly, RWY-dL-(Gd-DOTA)4 provided complementary enhancement MR signals to the clinical available hepatobiliary MR contrast agent gadoxetate disodium Gd-EOB-DTPA. Additionally, RWY-dL-(Gd-DOTA)4 showed minimal gadolinium retention in normal tissues and organs at 48 h post-injection. CONCLUSION: These findings potentiate the use of RWY-dL-(Gd-DOTA)4 for the MRI of HCC to improve the diagnosis of HCC.

2.
ACS Omega ; 4(13): 15560-15566, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31572857

RESUMO

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer deaths worldwide. Integrin α6 is overexpressed in all stages of CRC which makes it a potential diagnostic biomarker for CRC. Previously, we identified an integrin α6-targeted peptide CRWYDENAC (dubbed RWY) using phage display technology and employed it for nasopharyngeal carcinoma specific nanotherapeutics. In this study, we developed a radiotracer, 18F-RWY, based on this integrin α6-targeted RWY peptide for positron emission tomography (PET) imaging of CRC. Integrin α6 was overexpressed on several CRC cells including HT29 cells where the biotin-labeled RWY peptide colocalized with integrin α6. 18F-RWY PET imaging was performed on subcutaneous, chemically induced, and genetically engineered CRC mice. 18F-RWY generated high PET signals in subcutaneous HT29 tumors, and the tumor uptake of 18F-RWY was reduced by a blocking study using nonradio-labeled RWY. Moreover, 18F-RWY PET imaging enabled detection of CRC in chemically induced and genetically engineered CRC mice. The overexpression of integrin α6 in tumor tissues isolated from chemically induced and genetically engineered CRC mice was confirmed. These results demonstrate the potential clinical application of 18F-RWY for PET imaging of CRC.

4.
J Control Release ; 310: 11-21, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31400382

RESUMO

Integrin α6 emerges to be a diagnostic biomarker for hepatocellular carcinoma (HCC). Here, we translated our previously identified integrin α6 targeted peptide RWY into a positron emission tomography (PET) tracer 18F-RWY for the detection of HCC lesions in following four HCC mouse models including subcutaneous, orthotopic, genetically engineered and chemical induced HCC mice. 18F-RWY produced high PET signals in liver tumor tissues that were reduced by blocking studies using nonradiolabeled RWY peptide. We compared the integrin α6 targeted PET tracer 18F-RWY with the integrin αvß3-targeted PET tracer 18F-3PRGD2 and the clinical PET tracer 18F-FDG in chemical induced HCC mice. Among 12 HCC identified by enhanced magnetic resonance imaging (MRI) with hepatocellular specific gadoxetate disodium Gd-EOB-DTPA, the sensitivities of 18F-RWY, 18F-3PRGD2 and 18F-FDG were approximately 92%, 73% and 50% while the tumor-to-liver ratios were 4.36 ±â€¯1.41, 1.97 ±â€¯0.43 and 1.63 ±â€¯0.23 respectively. Additionally, PET imaging with the integrin α6 targeted 18F-RWY enabled to visualize small HCC lesions with diameters approximately 0.2 cm that was hard to be distinguished from surround hepatic vascular by enhanced MRI with Gd-EOB-DTPA. These findings potentiate the use of integrin α6 targeted PET tracer 18F-RWY for the detection of HCC.

5.
J Control Release ; 281: 178-188, 2018 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-29777796

RESUMO

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.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Peptídeos/metabolismo , Compostos Radiofarmacêuticos/química , ATPase Trocadora de Sódio-Potássio/metabolismo , Animais , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Linhagem Celular Tumoral , Feminino , Radioisótopos de Flúor , Xenoenxertos , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Camundongos Endogâmicos C57BL , Imagem Óptica/métodos , Tomografia por Emissão de Pósitrons/métodos , Subunidades Proteicas/metabolismo
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