Theranostics 2019; 9(16):4597-4607. doi:10.7150/thno.35322 This issue

Research Paper

Point-of-care Ratiometric Fluorescence Imaging of Tissue for the Diagnosis of Ovarian Cancer

Xiaobo Zhou1, Yawei Liu1, Qiyu Liu2, Luzhe Yan3, Meng Xue1, Wei Yuan1, Mei Shi1, Wei Feng1, Congjian Xu2✉, Fuyou Li1✉

1. Department of Chemistry & State Key Laboratory of Molecular Engineering of Polymers & Institute of Biomedicine Science, Fudan University, Shanghai 200433, China
2. Department of Obstetrics and Gynecology of Shanghai Medical School & Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases & Obstetrics and Gynecology Hospital of Fudan University, Fudan University Shanghai 200011, China
3. The High School Affiliated to Renmin University of China, Beijing 100080, China

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Citation:
Zhou X, Liu Y, Liu Q, Yan L, Xue M, Yuan W, Shi M, Feng W, Xu C, Li F. Point-of-care Ratiometric Fluorescence Imaging of Tissue for the Diagnosis of Ovarian Cancer. Theranostics 2019; 9(16):4597-4607. doi:10.7150/thno.35322. Available from https://www.thno.org/v09p4597.htm

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Abstract

Graphic abstract

During a minimally invasive tumor resection procedure, it is still a challenge to rapidly and accurately trace tiny malignant tumors in real time. Fluorescent molecular imaging is considered an efficient method of localizing tumors during surgery due to its high sensitivity and biosafety. On the basis of the fact that γ-glutamyltranspeptidase (GGT) is overexpressed in ovarian cancer, we herein designed a highly sensitive ratiometric fluorescent GGT-responsive probe Py-GSH for rapid tumor detection.

Methods: The GGT response probe (Py-GSH) was constructed by using GSH group as a response group and pyrionin B as a fluorescent reporter. Py-GSH was characterized for photophysical properties, response speed and selectivity of GGT and response mechanism. The anti-interference ability of ratiometric probe Py-GSH to probe concentration and excitation power was evaluated both in vitro and in tissue. The biocompatibility and toxicity of the ratiometric probe was examined using cytoxicity test. The GGT levels in different lines of cells were determined by ratiometric fluorescence imaging and cytometry analysis.

Results: The obtained probe capable to rapidly monitored GGT activity in aqueous solution with 170-fold ratio change. By ratiometric fluorescence imaging, the probe Py-GSH was also successfully used to detect high GGT activity in solid tumor tissues and small peritoneal metastatic tumors (~1 mm in diameter) in a mouse model. In particular, this probe was further used to determine whether the tissue margin following clinical ovarian cancer surgery contained tumor.

Conclusion: In combination of ratiometric fluorescence probes with imaging instrument, a point-of-care imaging method was developed and may be used for surgical navigation and rapid diagnosis of tumor tissue during clinical tumor resection.

Keywords: ovarian cancer detection, γ-glutamyltranspeptidase, point-of-care detection, ratiometric fluorescence imaging