Sensitive β-galactosidase-targeting fluorescence probe for visualizing small peritoneal metastatic tumours in vivo.

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.

• Authors: Daisuke Asanuma, Masayo Sakabe, Mako Kamiya, Kyoko Yamamoto, Jun Hiratake, Mikako Ogawa, Nobuyuki Kosaka, Peter L Choyke, Tetsuo Nagano, Hisataka Kobayashi, Yasuteru Urano
• Journal: Nature communications (Nat Commun) Vol. 6 Pg. 6463 (Mar 13 2015) ISSN: 2041-1723 [Electronic] England
• PMID: 25765713 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fluorescent Dyes
• beta-Galactosidase

Topics

• 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, pathology)
• Peritoneal Neoplasms (diagnosis, secondary)
• beta-Galactosidase (metabolism)