Evaluation of Two Optical Probes for Imaging the Integrin αvβ6- In Vitro and In Vivo in Tumor-Bearing Mice.
切换为英文Abstract:
PURPOSE:The purpose of this study was to develop and evaluate two αvβ6-targeted fluorescent imaging agents. The integrin subtype αvβ6 is significantly upregulated in a wide range of epithelial derived cancers, plays a key role in invasion and metastasis, and expression is often located at the invasive edge of tumors. αvβ6-targeted fluorescent imaging agents have the potential to guide surgical resection leading to improved patient outcomes. Both imaging agents were based on the bi-PEGylated peptide NH2-PEG28-A20FMDV2-K16R-PEG28 (1), a peptide that has high affinity and selectivity for the integrin αvβ6: (a) 5-FAM-X-PEG28-A20FMDV2-K16R-PEG28 (2), and (b) IRDye800-PEG28-A20FMDV2-K16R-PEG28 (3). PROCEDURES:Peptides were synthesized using solid-phase peptide synthesis and standard Fmoc chemistry. Affinity for αvβ6 was evaluated by ELISA. In vitro binding, internalization, and localization of 2 was monitored using confocal microscopy in DX3puroβ6 (αvβ6+) and DX3puro (αvβ6-) cells. The in vivo imaging and ex vivo biodistribution of 3 was evaluated in three preclinical mouse models, DX3puroβ6/DX3puro and BxPC-3 (αvβ6+) tumor xenografts and a BxPC-3 orthotopic pancreatic tumor model. RESULTS:Peptides were obtained in > 99% purity. IC50 values were 28 nM (2) and 39 nM (3). Rapid αvβ6-selective binding and internalization of 2 was observed. Fluorescent intensity (FLI) measurements extracted from the in vivo images and ex vivo biodistribution confirmed uptake and retention of 3 in the αvβ6 positive subcutaneous and orthotopic tumors, with negligible uptake in the αvβ6-negative tumor. Blocking studies with a known αvβ6-targeting peptide demonstrated αvβ6-specific binding of 3. CONCLUSION:Two fluorescence imaging agents were developed. The αvβ6-specific uptake, internalization, and endosomal localization of the fluorescence agent 2 demonstrates potential for targeted therapy. The selective uptake and retention of 3 in the αvβ6-positive tumors enabled clear delineation of the tumors and surgical resection indicating 3 has the potential to be utilized during image-guided surgery.
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MOLECULAR IMAGING AND BIOLOGY
MOL IMAGING BIOL
最新影响因子:3.484 | 期刊ISSN:1536-1632 | CiteScore:3.07 |
出版周期:Bimonthly | 是否OA:YES | 出版年份:2002 |
期刊官方网址:http://www.springer.com/medicine/radiology/journal/11307
自引率:4.10% | 研究方向:医学-核医学 |
出版地区:UNITED STATES |
SCI期刊coverage:Science Citation Index Expanded(科学引文索引扩展)
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MOLECULAR IMAGING AND BIOLOGY 期刊简介
英文简介:
Molecular Imaging and Biology (MIB) is the official journal of the Academy of Molecular Imaging. MIB invites original research contributions on the utilization of molecular imaging in problems of relevance in biology and medicine. The primary objective of the journal is to provide a forum for the discovery of molecular mechanisms of health and disease through the use of imaging techniques.
中文简介:(来自Google、百度翻译)
分子成像与生物学(MIB)是分子成像学会的官方期刊。MIB邀请在生物学和医学相关问题上利用分子成像的原始研究贡献。该杂志的主要目标是通过使用成像技术为发现健康和疾病的分子机制提供一个论坛。
MOLECULAR IMAGING AND BIOLOGY 期刊中科院评价数据
最新中科院分区
大类(学科) | 小类(学科) | 学科排名 |
医学 |
RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING (核医学) 2区 |
24/129 |
最新公布的期刊年发文量
年度总发文量 | 年度论文发表量 | 年度综述发表量 |
105 | 101 | 4 |
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MOLECULAR IMAGING AND BIOLOGY 期刊CiteScore评价数据
最新CiteScore值
引文计数(2018)
文献(2015-2017)
950次引用
309篇文献
CiteScore排名
序号 | 类别 | 排名 | 百分位 |
1 |
大类(学科):Medicine
小类(学科):Oncology
|
#98/325
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2 |
大类(学科):Medicine
小类(学科):Radiology, Nuclear Medicine and Imaging
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#31/270
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|
3 |
大类(学科):Biochemistry, Genetics and Molecular Biology
小类(学科):Cancer Research
|
#84/191
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