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Here we focus on \u03b2-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-\u03b2Gal, in which the optimized intramolecular spirocyclic function affords &gt;1,400-fold fluorescence enhancement on activation. We confirm that HMRef-\u03b2Gal sensitively detects intracellular \u03b2-galactosidase activity in several ovarian cancer lines. <jats:italic>In vivo<\/jats:italic>, this probe visualizes metastases as small as &lt;1\u2009mm 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.<\/jats:p>","DOI":"10.1038\/ncomms7463","type":"journal-article","created":{"date-parts":[[2015,3,13]],"date-time":"2015-03-13T10:03:17Z","timestamp":1426240997000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":420,"title":["Sensitive \u03b2-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo"],"prefix":"10.1038","volume":"6","author":[{"given":"Daisuke","family":"Asanuma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayo","family":"Sakabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mako","family":"Kamiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Hiratake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikako","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuyuki","family":"Kosaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Choyke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Nagano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisataka","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuteru","family":"Urano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,3,13]]},"reference":[{"key":"BFncomms7463_CR1","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1023\/A:1023791229361","volume":"22","author":"CP Carmignani","year":"2003","unstructured":"Carmignani, C. 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