A Targeted Folate Receptor-α Near-infrared Fluorescent Agent Used for in Vitro Diagnosis of Endometrial Cytology

Background Endometrial cancer is the second-most prevalent cancer after breast cancer. Endometrial cytology test is a new diagnosis method for endometrial lesions. However, some unresolved issues limited the application of endometrial cytology test (ECT) in early diagnosis and screening of endometrial cancer. Evidence suggests that FRα is overexpressed in various solid tumors such as endometrial cancer, breast carcinoma, ovarian cancer and so on. Based on the expression of FR-α, the agent used in intraoperative imaging, FRα-targeting antibody drugs and diagnosis were developed previously. Nevertheless, research regarding agents used in the diagnosis of endometrial cancer is rarely carried out yet. Methods To obtain a promising and efficient method for in vitro and screening diagnosis of endometrial cytology, we performed the synthesis and evaluation of the new near-infrared targeting fluorescent dye folic acid-ZW800-1 (ZW-FA) and to explore its potential feasibility for in vitro diagnosis of endometrial cancer. Characterisation and Folate receptor-α (FR-α) targeting verification of ZW-FA were performed first and 92 patients were recruited, after liquid-based cytology preparations, during a 15-month period. ZW-FA and Hematoxylin-Eosin (H&E) staining were performed on all cytological slides successively; the histological diagnoses were regarded as the gold standard for ROC curve analysis. Results The cut-off value of ZW-FA fluorescence intensity is 62.9745; the sensitivity (Se), specificity (Sp), false-negative rate (FNR), false-positive rate (FPR), positive predictive value (PV+) percentage and negative predictive value (PV–) of the ZW-FA method are 84.6%, 85.2%, 15.4%,14.8%, 93.2% and 69.7%, respectively. Conclusions ZW-FA is potentially efficient for in vitro diagnosis of endometrial lesions based on the FR-α expression level of different endometrial lesions. This research offers a promising and efficient method for in vitro and screening diagnosis of endometrial cytology. Trial registration: ChiCTR1800020123. Registered December 15, 2018.