RRC ID 67419
著者 Asanuma D, Sakabe M, Kamiya M, Yamamoto K, Hiratake J, Ogawa M, Kosaka N, Choyke PL, Nagano T, Kobayashi H, Urano Y.
タイトル Sensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo.
ジャーナル Nat Commun
Abstract Fluorescence-guided diagnostics is one of the most promising approaches for facile detection of cancer in situ. Here we focus on β-galactosidase, which is overexpressed in primary ovarian cancers, as a molecular target for visualizing peritoneal metastases from ovarian cancers. As existing fluorescence probes are unsuitable, we have designed membrane-permeable HMRef-βGal, in which the optimized intramolecular spirocyclic function affords >1,400-fold fluorescence enhancement on activation. We confirm that HMRef-βGal sensitively detects intracellular β-galactosidase activity in several ovarian cancer lines. In vivo, this probe visualizes metastases as small as <1 mm in diameter in seven mouse models of disseminated human peritoneal ovarian cancer (SHIN3, SKOV3, OVK18, OVCAR3, OVCAR4, OVCAR5 and OVCAR8). Because of its high brightness, real-time detection of metastases with the naked eye is possible. Endoscopic fluorescence detection of metastases is also demonstrated. The results clearly indicate preclinical potential value of the probe for fluorescence-guided diagnosis of peritoneal metastases from ovarian cancers.
巻・号 6
ページ 6463
公開日 2015-3-13
DOI 10.1038/ncomms7463
PII ncomms7463
PMID 25765713
PMC PMC4382686
MeSH Animals Disease Models, Animal Endoscopy Female Fluorescent Dyes / chemistry* Gene Expression Regulation, Neoplastic Humans Mice Mice, Inbred BALB C Microscopy, Fluorescence Neoplasm Metastasis Ovarian Neoplasms / diagnosis* Ovarian Neoplasms / pathology Peritoneal Neoplasms / diagnosis* Peritoneal Neoplasms / secondary beta-Galactosidase / metabolism*
IF 12.121
リソース情報
ヒト・動物細胞 NIH:OVCAR-3(RCB2135) OVK18(RCB1903)