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

• Asanuma, Daisuke

• Sakabe, Masayo

• Kamiya, Mako

• Yamamoto, Kyoko

• 平竹, 潤

• Ogawa, Mikako

• Kosaka, Nobuyuki

• Choyke, Peter L.

• Nagano, Tetsuo

• Kobayashi, Hisataka

• Urano, Yasuteru

抄録

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.

収録刊行物

• Nature Communications

  Nature Communications 6 2015-01-01

  Nature Publishing Group

キーワード

• Biological sciences
• Biotechnology
• Cancer

詳細情報

• CRID: 1050845760760122368
• NII論文ID: 120005743656
• ISSN: 20411723
• HANDLE: 2433/210215
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles