4.6 Article

Near-Infrared Fluorescent Agent for In Vitro Screening of Endometrial Cancer and Precancerous Lesions

Journal

FRONTIERS IN ONCOLOGY
Volume 11, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2021.713583

Keywords

endometrial cancer; FR-alpha; in vitro diagnosis; near-infrared targeting fluorescent dye; ZW-FA

Categories

Funding

  1. Major Basic Research Project of Natural Science of Shaanxi Provincial Science and Technology Department [2018JM7073, 2017ZDJC-11]
  2. Clinical Research Award of the First Affiliated Hospital of Xi'an Jiaotong University, China [XJTU1AF-2018-017, XJTU1AF-CRF-2019-002]
  3. Key Research and Development Project of Shaanxi Provincial Science and Technology Department [2017ZDXM-SF-068, 2019QYPY-138]
  4. Shaanxi Provincial Collaborative Technology Innovation Project [2017XT-026, 2018XT-002]
  5. Medical Research Project of Xi'an Social Development Guidance Plan [2017117SF/YX011-3]

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The study focused on synthesizing a new fluorescent agent for screening of endometrial cancer and precancerous change, which showed promising results in clinical validation, indicating that ZW-FA could be an effective cytologic strategy for in vitro diagnosis.
The lack of cytopathologists delays the advancement of screening for endometrial cancer. It was urgent to develop a new dye for rapid diagnosis. Our study aimed to synthesize a targeted folate receptor-a near-infrared (NIR) fluorescent agent, folic acid-zwitterionic NIR fluorophore (ZW-FA), and explore the feasibility for screening of endometrial cancer and precancerous change. Folic acid was conjugated with zwitterionic NIR fluorophore. The preparation of ZW-FA was validated by H-1 NMR, mass spectrometric, ultraviolet spectra and fluorescence spectra. ZW-FA was incubated with endometrial cytology samples obtained from patients who underwent dilation and curettage or total hysterectomy. Diagnostic utility was calculated by applying laser confocal microscope, Image-J and statistical models, such as enumeration, receiver operating characteristic curve, logistic regression, support vector machine and decision tree were used. The purity of ZW-FA was > 95% determined by H-1 NMR. ZW-FA had the strongest absorption peak at 633 nm in ultraviolet spectra. Photostability of ZW-FA was over 8 hours. In clinical validation, a total of 92 patients were enrolled. The cut-off value of ZW-FA was 49 in enumeration, which was used to distinguish the type of samples. Indicators about diagnostic utility are as follows: sensitivity 90.77%, specificity 62.96%, false-positive rate 37.04%, false-negative rate 9.23%, positive predictive value 85.51% and negative predictive value 73.91%. The samples processed by ZW-FA did not affect further Hematoxylin-Eosin staining and pathological diagnosis. It was an effective cytologic strategy for in vitro diagnosis of endometrial cancer and precancerous change by using ZW-FA.

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