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一种用于乳腺癌检测的靶向MT1-MMP的放射性标记肽基探针的研发

Development of a Radiolabeled Peptide-Based Probe Targeting MT1-MMP for Breast Cancer Detection.

作者信息

Min Kaiyin, Ji Bin, Zhao Min, Ji Tiefeng, Chen Bin, Fang Xuedong, Ma Qingjie

机构信息

Department of Nuclear Medicine, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

出版信息

PLoS One. 2015 Oct 5;10(10):e0139471. doi: 10.1371/journal.pone.0139471. eCollection 2015.

DOI:10.1371/journal.pone.0139471
PMID:26437463
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4593522/
Abstract

Breast cancer is one of the most frequent and aggressive primary tumors among women of all races. Matrix metalloproteinase (MMPs), a family of zinc- and calcium-dependent secreted or membrane anchored endopeptidases, is overexpressed in varieties of diseases including breast cancer. Therefore, noninvasive visualization and quantification of MMP in vivo are of great interest in basic research and clinical application for breast cancer early diagnosis. Herein, we developed a 99mTc labeled membrane type I matrix metalloproteinase (MT1-MMP) specific binding peptide, [99mTc]-(HYNIC-AF7p)(tricine)(TPPTS), for in vivo detection of MDA-MB-231 breast tumor by single photon emission computed tomography (SPECT). [99mTc]-(HYNIC-AF7p)(tricine)(TPPTS) demonstrated nice biostability and high MT1-MMP binding affinity in vitro and in vivo. Tumor-to-muscle ratio was found to reach to the highest (4.17±0.49) at 2 hour after intravenously administration of [99mTc]-(HYNIC-AF7P)(tricine)(TPPTS) into MDA-MB-231 tumor bearing mice. Overall, [99mTc]-(HYNIC-AF7P)(tricine)(TPPTS) demonstrated great potential for MT1-MMP targeted detection in vivo and it would be a promising molecular imaging probe that are probably beneficial to breast cancer early diagnoses.

摘要

乳腺癌是所有种族女性中最常见且侵袭性最强的原发性肿瘤之一。基质金属蛋白酶（MMPs）是一类依赖锌和钙的分泌型或膜锚定型内肽酶家族，在包括乳腺癌在内的多种疾病中均有过表达。因此，MMP在体内的无创可视化和定量分析在乳腺癌早期诊断的基础研究和临床应用中备受关注。在此，我们开发了一种99mTc标记的膜型I基质金属蛋白酶（MT1-MMP）特异性结合肽[99mTc]-(HYNIC-AF7p)(tricine)(TPPTS)，用于通过单光子发射计算机断层扫描（SPECT）对MDA-MB-231乳腺肿瘤进行体内检测。[99mTc]-(HYNIC-AF7p)(tricine)(TPPTS)在体外和体内均表现出良好的生物稳定性和高MT1-MMP结合亲和力。在给荷MDA-MB-231肿瘤小鼠静脉注射[99mTc]-(HYNIC-AF7P)(tricine)(TPPTS)后2小时，肿瘤与肌肉的比值达到最高（4.17±0.49）。总体而言，[99mTc]-(HYNIC-AF7P)(tricine)(TPPTS)在体内MT1-MMP靶向检测方面显示出巨大潜力，它将是一种有前景的分子成像探针，可能对乳腺癌早期诊断有益。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/f23e7d5f56ee/pone.0139471.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/73e1b1cf57cb/pone.0139471.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/19b20d9315e4/pone.0139471.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/3e56233ad258/pone.0139471.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/3582abab6622/pone.0139471.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/26b31d7b7114/pone.0139471.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/f23e7d5f56ee/pone.0139471.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/73e1b1cf57cb/pone.0139471.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/19b20d9315e4/pone.0139471.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/3e56233ad258/pone.0139471.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/3582abab6622/pone.0139471.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/26b31d7b7114/pone.0139471.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cbf0/4593522/f23e7d5f56ee/pone.0139471.g006.jpg

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