文章基本信息

标题：Development of a Radiolabeled Probe for Detecting Membrane Type-1 Matrix Metalloproteinase on Malignant Tumors
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作者：Takashi Temma ; Kohei Sano ; Yuji Kuge 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2009
卷号：32
期号：7
页码：1272-1277
DOI：10.1248/bpb.32.1272
出版社：The Pharmaceutical Society of Japan
摘要：Membrane type-1 matrix metalloproteinase (MT1-MMP) expressed on the tumor cell surface activates pro-MMP-2 and pro-MMP-13 to exacerbate the malignancy, suggesting its suitability as a target molecule for diagnosis by in vivo molecular imaging. Thus, we prepared radiolabeled anti-MT1-MMP monoclonal antibody (mAb) as a novel radiolabeled probe for detecting MT1-MMP in vivo and evaluated its usefulness in breast tumor-bearing rodents. ^99mTc-anti-MT1-MMP mAb was prepared using HYNIC as a bifunctional chelating agent and immunoreactivity was evaluated by flow cytometry. MT1-MMP expression in breast carcinoma cells (rat: Walker-256 and MRMT-1, mouse: FM3A) was measured by Western blotting. In vivo biodistribution was examined for 48 h using tumor-implanted rodents followed by estimation of radiation absorbed by a standard quantitation platform Organ Level Internal Dose Assessment (OLINDA). ^99mTc-anti-MT1-MMP mAb was obtained with 84% immunoreactivity to MT1-MMP and more than 92% radiochemical purity. MT1-MMP was highly expressed in all malignant cells. Tumor radioactivity increased with time after administration and reached 3 to 5 times higher values at 24 h post-injection than those at 1 h. Other organs, including the stomach, showed decreasing values over time. Tumor to blood ratios increased with time and reached more than 1.3 at 48 h. The effective dose was <5.0 μSv/MBq. The results suggest that ^99mTc-anti-MT1-MMP mAb is a promising probe for future diagnosis of breast tumors by in vivo nuclear medical imaging.
关键词：membrane type-1 matrix metalloproteinase;breast tumor;non-invasive imaging;single photon emission computed tomography