放射性碘标记的低ph插入肽变体3在小鼠乳腺癌模型中的体内分布和治疗效果。

IF 2.2 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS
Molecular Imaging Pub Date : 2022-07-04 eCollection Date: 2022-01-01 DOI:10.1155/2022/7456365
Min Zhang, Yue Xi, Hong Chen, Wangxi Hai, Biao Li
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引用次数: 2

摘要

目的:细胞外酸度是高度侵袭性乳腺癌(BC)的标志。低ph插入肽(pHLIPs)靶向酸性肿瘤微环境。本研究评估了放射性碘标记的pHLIP变体3 (Var3)在BC小鼠模型中的分布和治疗效果。方法:体外观察不同pH值下异硫氰酸荧光素(FITC)-或放射性碘-125 (125I)标记的var3 - philips与MDA-MB-231、4T1和SK-BR-3 BC细胞株的结合情况。采用显微spect /CT成像技术分析125i标记的Var3-pHLIP和野生型(WT-) pHLIP在荷瘤小鼠体内的分布。通过相对肿瘤体积测定和免疫组化分析评价放射性碘-131 (131I)标记的var3 - phillip对MDA-MB-231异种移植物的治疗效果。结果:FITC-或125i标记的Var3-pHLIP与肿瘤细胞的结合能力随着ph的降低而增强,125I-Var3-pHLIP在注射后24 h和48 h的肿瘤与背景比显示出最好的成像对比。注射后2 h, MDA-MB-231异种移植物对125I-Var3-pHLIP的摄取明显高于125I-WT-pHLIP(3.76±0.37比2.87±0.60%ID/g, p = 0.046)。131I- var3 - philips处理组MDA-MB-231异种移植物的相对肿瘤体积显著低于var3 - philips处理组(p = 0.027)、131I (p = 0.001)和生理盐水处理组(p < 0.001)。131I-Var 3- phlip组Ki67表达较低,caspase 3表达较高。结论:放射性碘标记的var3 - philips在酸性环境下能有效靶向BC细胞,并通过电离辐射抑制MDA-MB-231异种移植物的生长。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast Cancer.

In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast Cancer.

In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast Cancer.

In Vivo Distribution and Therapeutic Efficacy of Radioiodine-Labeled pH-Low Insertion Peptide Variant 3 in a Mouse Model of Breast Cancer.

Purpose: Extracellular acidity is a marker of highly aggressive breast cancer (BC). pH-low insertion peptides (pHLIPs) target the acidic tumor microenvironment. This study evaluates the distribution and therapeutic efficacy of radioiodine-labeled pHLIP variant 3 (Var3) in a mouse model of BC.

Methods: The binding of fluorescein isothiocyanate (FITC)- or radioiodine-125 (125I) labeled Var3-pHLIP to MDA-MB-231, 4T1, and SK-BR-3 BC cell lines under different pH values was evaluated in vitro. The distribution of 125I-labeled Var3-pHLIP and wild-type- (WT-) pHLIP in tumor-bearing mice was analyzed in vivo using micro-SPECT/CT imaging. The therapeutic efficacy of radioiodine-131 (131I)-labeled Var3-pHLIP in MDA-MB-231 xenografts was evaluated by relative tumor volume measurement and immunohistochemical analysis.

Results: The binding ability of FITC- or 125I-labeled Var3-pHLIP to tumor cells increased with the decrease in pH. The tumor-to-background ratio of 125I-Var3-pHLIP in BC xenografts showed the best imaging contrast at 24 h or 48 h postinjection. The uptake of 125I-Var3-pHLIP in MDA-MB-231 xenografts at 2 h postinjection was significantly higher than that of 125I-WT-pHLIP (3.76 ± 0.37 vs. 2.87 ± 0.60%ID/g, p = 0.046). The relative tumor volume in MDA-MB-231 xenografts was significantly lower in the 131I-Var3-pHLIP-treated group than in the groups treated with Var3-pHLIP (p = 0.027), 131I (p = 0.001), and saline (p < 0.001). The 131I-Var 3-pHLIP group presented a lower expression of Ki67 and a higher expression of caspase 3.

Conclusion: Radioiodine-labeled Var3-pHLIP effectively targeted BC cells in an acidic environment and inhibited the growth of MDA-MB-231 xenografts by ionizing radiation.

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来源期刊
Molecular Imaging
Molecular Imaging Biochemistry, Genetics and Molecular Biology-Biotechnology
自引率
3.60%
发文量
21
期刊介绍: Molecular Imaging is a peer-reviewed, open access journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. This serves both the scientific and clinical communities by disseminating novel results and concepts relevant to the biological study of normal and disease processes in both basic and translational studies ranging from mice to humans.
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