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タイトル: Radioiodinated Peptidic Imaging Probes for in Vivo Detection of Membrane Type-1 Matrix Metalloproteinase in Cancers.
著者: Kondo, Naoya
Temma, Takashi
Shimizu, Yoichi  kyouindb  KAKEN_id
Ono, Masahiro  kyouindb  KAKEN_id
Saji, Hideo
著者名の別形: 天満, 敬
佐治, 英郎
キーワード: membrane type-1 matrix metalloproteinase (MT1-MMP)
peptide
n vivo imaging
発行日: 2015
出版者: Pharmaceutical Society of Japan
誌名: Biological & pharmaceutical bulletin
巻: 38
号: 9
開始ページ: 1375
終了ページ: 1382
抄録: Membrane type-1 matrix metalloproteinase (MT1-MMP) plays pivotal roles in tumor progression and metastasis, and holds great promise as an early biomarker for malignant tumors. Therefore, the ability to evaluate MT1-MMP expression could be valuable for molecular biological and clinical studies. For this purpose, we aimed to develop short peptide-based nuclear probes because of their facile radiosynthesis, chemically uniform structures, and high specific activity, as compared to antibody-based probes, which could allow them to be more effective for in vivo MT1-MMP imaging. To the best of our knowledge, there have been no reports of radiolabeled peptide probes for the detection of MT1-MMP in cancer tissues. In this study, we designed and prepared four probes which consist of a MT1-MMP-specific binding peptide sequence (consisting of L or D amino acid isomers) and an additional cysteine (at the N or C-terminus) for conjugation with N-(m-[(123/125)I]iodophenyl) maleimide. We investigated probe affinity, probe stability in mice plasma, and probe biodistribution in tumor-bearing mice. Finally, in vivo micro single photon emission computed tomography (SPECT) imaging and ex vivo autoradiography were performed. Consequently, [(123)I]I-DC, a D-form peptide probe radioiodinated at the C-terminus, demonstrated greater than 1000-fold higher specific activity than previously reported antibody probes, and revealed comparably moderate binding affinity. [(125)I]I-DC showed higher stability as expected, and [(123)I]I-DC successfully identified MT1-MMP expressing tumor tissue by SPECT imaging. Furthermore, ex vivo autoradiographic analysis revealed that the radioactivity distribution profiles corresponded to MT1-MMP-positive areas. These findings suggest that [(123)I]I-DC is a promising peptide probe for the in vivo detection of MT1-MMP in cancers.
著作権等: © 2015 The Pharmaceutical Society of Japan
URI: http://hdl.handle.net/2433/202618
DOI(出版社版): 10.1248/bpb.b15-00314
PubMed ID: 26328493
出現コレクション:学術雑誌掲載論文等

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