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Fluorescence-labeled pH-low insertion peptide imaging of the acid microenvironment of breast tumor / 中华核医学与分子影像杂志
Chinese Journal of Nuclear Medicine and Molecular Imaging ; (6): 488-493, 2019.
Artigo em Chinês | WPRIM | ID: wpr-755295
ABSTRACT
Objective Fluorescence-labeled pH-low insertion peptide ( pHLIP ) imaging was used to analyze in vitro acidophilic characteristic of pHLIP and its dynamic distribution in the transplanted breast tumor models. Methods The red fluorescent dye Rhodamine B ( B-pHLIP ) and near-infrared fluorescent dye Cy5 ( Cy5-pHLIP ) were respectively labeled at the hydroxyl terminal of pHLIP for imaging in vitro and in vivo. The fluorescent intensity in the MDA-MB-231 breast cancer cells and the cell vitality were analyzed under different pH values (7.8, 7.4, 7.0, 6.6). In vivo dynamic fluorescent distribution, fluorescent intensi-ties and tumor/non-tumor ( T/NT) ratios in the regions of interest of tumor and normal organs at different time points (2 h, 24 h, 3 d, 7 d) were observed or calculated, and then fluorescence imaging of the isolated tis-sues was finally performed. One-way analysis of variance and least significant difference t test were used to analyze the data. Results Relative fluorescent intensity of B-pHLIP in the MDA-MB-231 cells at pH 6.6, 7.0, 7.4 and 7.8 were (100.00±9.70)%, (69.90±5.50)%, (19.80±1.40)% and (0.40±0.04)%, re-spectively. There were significant differences between pH 6. 6 group and other groups ( F=230. 504, t=5. 029-17.669, all P<0.05). pHLIP had no significant toxic effect on MDA-MB-231 cells. After Cy5-pHLIP injection in vivo, the fluorescent intensity of tumor in mice gradually decreased, but the T/NT ratios were stable (3.42±0.27, 3.00±1.23, 3.38±0.62 and 3.51±0.37 at 2 h, 24 h, 3 d and 7 d respectively;F=0.192, P>0. 05) . The ex vivo fluorescence distribution showed that Cy5-pHLIP had a higher uptake in the tumor tissue, and the large intestine also secreted a large amount of pHLIP. Conclusions The affinity be-tween pHLIP and tumor cell membrane is significantly increased in the extracellular acidic microenviron-ment. Cy5-pHLIP enables long-term and visual monitoring the tumor-targeted distribution of pHLIP in vivo. However, the high accumulation of pHLIP in the large intestine increases the interpretation complexity of tumor imaging.

Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Tipo de estudo: Estudo prognóstico Idioma: Chinês Revista: Chinese Journal of Nuclear Medicine and Molecular Imaging Ano de publicação: 2019 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Tipo de estudo: Estudo prognóstico Idioma: Chinês Revista: Chinese Journal of Nuclear Medicine and Molecular Imaging Ano de publicação: 2019 Tipo de documento: Artigo