Exploration of the application of the sprayed γ-GGT fluorescent probe for visual imaging of epithelial ovarian cancer: a pilot study

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Abstract Objective To evaluate the feasibility and accuracy of a sprayable γ-GGT fluorescent probe for visualizing epithelial ovarian cancer (EOC) across three hierarchical models (organoids, frozen sections, and ex vivo tissues), with a focus on optimizing its clinical applicability in intraoperative lesion detection. Methods This prospective study, leveraging a medical-engineering collaborative γ-GGT probe, was conducted in three phases: preliminary validation, ex vivo tissue optimization, and clinical validation. Initially, TCGA analysis and immunohistochemistry confirmed γ-GGT overexpression in epithelial ovarian cancer (EOC), with organoids and frozen sections employed to evaluate the probe’s specificity at both cellular and microstructural levels. Subsequently, fresh EOC tissues ( n = 42 lesions from 8 patients) were treated with varying concentrations of the probe (1 μM, 5 μM, or 10 μM) to ascertain the minimal effective concentration (10 μM) and the optimal observation window (1 min–1 h) using signal-to-background ratio (SBR) analysis. Finally, clinical validation involved imaging 27 lesions (< 0.3 cm) and adjacent normal tissues from 8 patients, assessing the probe’s sensitivity (96.3% true positive rate) and false-positive rates (3.7%). Results Initial validation in ovarian cancer organoids and frozen sections demonstrated precise colocalization of γ-GGT probe fluorescence with immunohistochemical staining (DAB), confirming target specificity at cellular and microstructural levels. In ex vivo tissues (42 lesions from 16 patients), the 10 μM probe concentration achieved superior signal-to-background ratios (SBR = 1.40 ± 0.17 for primary lesions, 1.32 ± 0.12 for omental metastases) compared to 1 μM (1.17 ± 0.08) and 5 μM (1.27 ± 0.10) concentrations ( P < 0.05). The probe consistently visualized lesions across all diameters (0.5 cm: SBR 1.40 ± 0.17; < 0.3 cm: SBR 1.41 ± 0.18; P > 0.05), with optimal imaging stability observed 1 min-1 h post-application (SBR range:1.26–1.29). Clinical validation in 27 sub-0.3 cm lesions demonstrated 96.3% sensitivity (26/27 true positives) and 81.5% macroscopic detection rate, with one false positive (3.7%) in normal peritoneal tissue. Immunohistochemistry confirmed γ-GGT membrane expression in 100% of cancerous lesions (42/42 experimental group, 26/27 validation group) versus absent expression in normal tissues. Univariate analysis identified preoperative serum γ-GGT levels (≥ 20 U/L: SBR 1.28 ± 0.13 vs < 20 U/L: 1.23 ± 0.18, P = 0.005) and treatment modality ( P = 0.001) as significant factors, though only treatment approach remained independently predictive in multivariate analysis ( P < 0.001). Conclusion The γ-GGT probe enables rapid, accurate EOC visualization at clinically relevant scales, with 10 μM concentration and 1 min–1 h window being optimal for intraoperative use. Hierarchical validation from cellular to tissue models underscores its translational potential.

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