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	Development of PEGylated peptide probes conjugated with (18)F-labeled BODIPY for PET/optical imaging of MT1-MMP activity.
掲載誌名	正式名：Journal of controlled release : official journal of the Controlled Release Society ISSNコード：0168-3659/1873-4995
掲載区分	国外
出版社	ELSEVIER SCIENCE BV
巻・号・頁	220(Pt A),pp.476-483
著者・共著者	Naoya Kondo,Takashi Temma,Jun Deguchi,Kohei Sano,Masahiro Ono,Hideo Saji
発行年月	2015/12/28
概要	Since the processing activity of the matrix metalloproteinase MT1-MMP regulates various cellular functions such as motility, invasion, growth, differentiation and apoptosis, precise in vivo evaluation of MT1-MMP activity in cancers can provide beneficial information for both basic and clinical studies. For this purpose, we designed a cleavable Positron Emission Tomography (PET)/optical imaging probe consisting of BODIPY650/665 and polyethylene glycol (PEG) conjugated to opposite ends of MT1-MMP substrate peptides. We used in vitro and in vivo fluorescence experiments to select suitable substrate peptide sequences and PEG sizes for the MT1-MMP probes and obtained an optimized structure referred to here as MBP-2k. Radiofluorinated MBP-2k ([(18)F]MBP-2k) was then successfully synthesized via an (18)F-(19)F isotopic exchange reaction in BODIPY650/665. After intravenous injection into mice with xenografted tumors, [(18)F]MBP-2k showed significantly higher accumulation in HT1080 tumors with high MT1-MMP activity than in A549 tumors that have low MT1-MMP activity. Moreover, PET images showed better contrast in HT1080 tumors. These results show that [(18)F]MBP-2k can be used as a hybrid PET/optical imaging agent and is a promising probe for non-invasive monitoring of MT1-MMP activity in cancers. This probe may also efficiently combine targeted tumor imaging with image-guided surgery that could be beneficial for patients in the future.
DOI	10.1016/j.jconrel.2015.11.012
PMID	26578437