論文種別	原著(症例報告除く)
言語種別	英語
査読の有無	査読あり
表題	Investigation of a MMP-2 Activity-Dependent Anchoring Probe for Nuclear Imaging of Cancer
掲載誌名	正式名：PLOS ONE ISSNコード：1932-6203
出版社	PUBLIC LIBRARY SCIENCE
巻・号・頁	9(7),pp.e102180
著者・共著者	Takashi Temma,Hirofumi Hanaoka,Aki Yonezawa,Naoya Kondo,Kohei Sano,Takeharu Sakamoto,Motoharu Seiki,Masahiro Ono,Hideo Saji
発行年月	2014/07
概要	Purpose: Since matrix metalloproteinase-2 (MMP-2) is an important marker of tumor malignancy, we developed an original drug design strategy, MMP-2 activity dependent anchoring probes (MDAP), for use in MMP-2 activity imaging, and evaluated the usefulness of this probe in in vitro and in vivo experiments. Methods: We designed and synthesized MDAP(1000), MDAP(3000), and MDAP(5000), which consist of 4 independent moieties: RI unit (111 In hydrophilic chelate), MMP-2 substrate unit (short peptide), anchoring unit (alkyl chain), and anchoring inhibition unit (polyethylene glycol (PEGn; where n represents the approximate molecular weight, n = 1000, 3000, and 5000). Probe cleavage was evaluated by chromatography after MMP-2 treatment. Cellular uptake of the probes was then measured. Radioactivity accumulation in tumor xenografts was evaluated after intravenous injection of the probes, and probe cleavage was evaluated in tumor homogenates. Results: MDAP(1000), MDAP(3000), and MDAP(5000) were cleaved by MMP-2 in a concentration-dependent manner. MDAP(3000) pretreated with MMP-2 showed higher accumulation in tumor cells, and was completely blocked by additional treatment with an MMP inhibitor. MDAP(3000) exhibited rapid blood clearance and a high tumor accumulation after intravenous injection in a rodent model. Furthermore, pharmacokinetic analysis revealed that MDAP(3000) exhibited a considerably slow washout rate from tumors to blood. A certain fraction of cleaved MDAP(3000) existed in tumor xenografts in vivo. Conclusions: The results indicate the possible usefulness of our MDAP strategy for tumor imaging.
DOI	10.1371/journal.pone.0102180
PMID	25010662