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. 2025 Mar 13;15:22. doi: 10.1186/s13550-025-01218-6

Novel GAL7-targeted fluorescent molecular imaging probe for high-grade squamous intraepithelial lesion and cervical cancer screening

Xiaohui Teng 1,3,#, Chu Tang 2,#, Kunshan He 3, Chunlin Chen 4,✉, Jie Tian 3,5,✉, Yang Du 3,6,✉
PMCID: PMC11906962  PMID: 40082314

Abstract

Background

Early detection and treatment are critical for improving the survival and prognosis of patients with cervical cancer. However, there is a notable scarcity of targeted imaging probes specifically designed to detect high-grade squamous intraepithelial lesions (HSIL) and cervical cancer. Our study aimed to address this gap by identifying and validating a targeted imaging probe for these conditions.

Results

Using bioinformatics data, we identified galectin-7 (GAL7) as highly expressed in patients with cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Immunohistochemical staining of biopsy samples from 30 HSIL and cervical cancer patients verified the high and specific expression of GAL7. Further validation was performed using mouse and human CESC cell lines and tumor xenografts, confirming the consistent expression of GAL7. Based on this finding, we synthesized a GAL7-specific antibody conjugated with FITC, creating the GAL7-FITC fluorescence imaging probe. Fluorescence molecular imaging revealed that GAL7-FITC exhibited specific binding to various CESC cell lines and xenograft mouse models. Additionally, the diagnostic capability of GAL7-FITC was demonstrated in fresh HSIL specimens from cervical cone excisions, validated through histopathology and immunohistochemical analysis.

Conclusions

Our study identified GAL7 as a specific target for CESC and successfully developed the GAL7-FITC fluorescence imaging probe. GAL7-FITC has shown promising potential for clinical application in the early detection of HSIL and CESC, providing rapid fluorescence imaging diagnosis without observable toxicity. This advancement may significantly enhance the accuracy and speed of cervical cancer diagnostics, ultimately improving patient outcomes.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13550-025-01218-6.

Keywords: GAL7, Fluorescent imaging probe, Cervical screening, Colposcopy

Introduction

Cervical cancer is a widespread malignant tumor that affects the lower reproductive tract in women [1]. It ranked fourth in terms of new cases and deaths among female cancers worldwide in 2020, with China accounting for over one-sixth of these cases. Early detection and treatment of cervical cancer are vital, as there is usually a prolonged high-grade squamous intraepithelial lesion (HSIL) stage before it develops. The current screening process involves colposcopy combined with testing using Lugol’s iodine, acetic acid, and biopsy [2]. However, traditional colposcopy is subjective and has limited sensitivity in detecting HSIL [3–6]. Biopsy is an invasive procedure that increases discomfort for patients, and pathology results take several days for diagnosis.

To improve accuracy and safety, there is a need for a real-time screening method that can provide accurate and immediate diagnosis during colposcopy. Fluorescence imaging using targeted tumor fluorescent dyes has shown promise in biomedical imaging [7]. Fluorescent molecular imaging (FMI) methods utilizing targeted tumor fluorescent dyes have gained extensive application in intraoperative tumor detection and staging [8–13]. Near-infrared (NIR) excitable probes have enabled non-invasive cancer imaging [14–16]. Various types of fluorescent agents have been developed for tumor targeting, including receptor-targeted NIR dyes [11, 17–21], small molecule agents [22], protein kinase imaging agents [23], and certain agents currently undergoing clinical trials [13]. It overcomes the limitations of single imaging techniques, improves sensitivity and accuracy [24–26]. Currently, fluorescence and cervical microscopy is being utilized by teams to perform multimodal imaging and detect cervical lesions. One study conducted by Thomas Reiner et al. was involved the examination of the molecular marker PARP 1 during colposcopy for cancer identification [27]. Wang et al. also explored the use of dual-mode fluorescence microscopy in combination with near-infrared fluorescent probe TMTP1-PEG4-ICG for the detection of cervical lesions [28]. Nevertheless, the existing research findings are only capable of distinguishing between normal cervical tissues and cervical cancer, difficult to differentiate between HSIL and a normal cervix. Furthermore, the absence of a reliable animal model for HSIL hinders the verification of the accuracy and safety of the probe, thereby placing limitations on the detection of potential malignant cervical lesions during colposcopy.

Recently, GAL7 has garnered attention for its role in tumorigenesis, despite ongoing debates about the precise mechanisms involved. Overexpression of GAL7 has been documented across various malignancies, including pancreatic cancer, esophageal squamous cell carcinoma, oral squamous cell carcinoma, hypopharyngeal squamous cell carcinoma, and laryngeal squamous cell carcinoma [29–32]. Studies suggest that GAL7 promotes tumor metastasis, particularly in cervical adenocarcinoma and hypopharyngeal/laryngeal squamous cell carcinoma, by enhancing matrix metalloproteinase-9 (MMP-9) expression via the p38 mitogen-activated protein kinase (MAPK) signaling pathway [29, 33]. Additionally, the downregulation of GAL7 in ovarian cancer cell lines has been shown to inhibit cell proliferation, emphasizing its role in tumor growth [34]. Cervical cancer currently lacks specific targets for identification. Galectin-7 (GAL7) belongs to the β-galactoside-binding protein family and plays a crucial role in modulating cellular interactions with the extracellular matrix. Various studies employing differential and in-situ hybridization techniques have consistently demonstrated GAL7’s specific expression in keratinizing cells, particularly within the stratified squamous epithelium [35]. GAL7 is primarily localized within the nuclei and cytoplasm of squamous epithelial cells [36–38].

In this study, we aimed to examine whether GAL7 is comparatively elevated in cervical lesions, including HSIL, compared to normal cervical epithelium; and utilized GAL7 as an imaging target to develop fluorescence imaging probe to examine its potential binding affinity towards HSIL. We successfully established an HSIL mouse model and validated the GAL7-FITC probe’s feasibility for rapid HSIL detection and cervical cancer diagnosis. Our research endeavors to achieve real-time fluorescence imaging of cervical lesion during colposcopy, offering prompt identification of cervical specimens obtained from biopsies or cone excisions, thereby enhancing the accuracy and timeliness of HSIL or cervical cancer detection. The integration of colposcopy and fluorescence multimodal imaging techniques represents a promising approach for real-time monitoring and expedited diagnosis of cervical lesions.

Materials and methods

Cell culture

In this study, three human cervical cancer cell lines (SiHa cells[RRID: CVCL_0032, ATCC], C-33 A cells[RRID: CVCL_1094, ATCC], and HeLa cells[RRID: CVCL_0030, ATCC]) and one human cervical epithelial cell line (H8 cells[CP-H059]) were utilized. The cell lines were obtained from Wuhan Punoise Life Technology Co., Ltd. and subjected to STR analysis to verify their authenticity. The cells were cultured in either MEM or DMEM medium (Thermo Fisher) supplemented with 10% fetal bovine serum (FBS) (Thermo Fisher) and 1% penicillin (Omacgene). MEM medium was utilized for SiHa and HeLa cells, whereas DMEM medium was used for C-33 A and H8 cells. Upon reaching 80–90% confluency, trypsin-EDTA (0.25% EDTA) (Thermo Fisher) was applied for cell passaging.

Animal models

Male and female BALB/c mice (6 weeks old, 18–20 g) were utilized for cohabitation breeding in order to establish the HSIL mouse model in the offspring. Starting from day 13 of pregnancy, diethylstilbestrol (ThermoFisher) dissolved in sesame oil was orally administered to female BALB/c mice at a daily dose of 120 µg/kg for 5 consecutive days until birth. Female offspring mice were sacrificed at 48–54 days of age after delivery. The uterus and cervix were dissected and subjected to H&E staining. The cervical lesions were diagnosed as HSIL under a microscope.

BALB/c-nude mice (6 weeks old, 18–20 g) were chosen for constructing xenograft models of cervical cancer (SiHa, C-33 A and HeLa) and an in-situ implantation model of squamous cell carcinoma (SiHa) in the cervix. A cell suspension containing 13 × 106 SiHa/C-33 A cells or 26 × 106 HeLa cells in 100 µL of PBS was subcutaneously injected into the right leg of the mice. The experiment was conducted when the tumors reached a diameter of 8–10 mm (approximately 25–30 days).

The mice were anesthetized with isoflurane (RWD Life Science). A cell suspension containing 4 × 106 SiHa cells in 25 µL of PBS was gently injected into the cervix of the mice. This injection procedure was repeated once daily for 7 consecutive days. The experiment was conducted when in-situ tumor formation with a diameter of 3–5 mm (approximately 30 days) was observed in the cervix. Construction and H&E staining validation of mouse models can be found in the Supplementary Information (SI) Fig. 1.

Fig. 1.

Fig. 1

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Schematic of the experimental procedure of targeted fluorescent probe GAL7-FITC for the targeted imaging and diagnosis of HSIL/cervical cancer. (a) Preclinical animal experiments. (b) Clinical imaging procedure of cone biopsy

Bioinformatics analysis database

We acquired the dataset from the Gene Expression Profiling Interactive Analysis (GEPIA, http://gepia.cancerpku.cn/index.html) and conducted a comparative analysis of GAL7 expression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) with that in normal cervical tissue cells.

Western blot

Cells (SiHa, C-33 A, HeLa, or H8) were treated with precooled RIPA lysis buffer (Servicebio) supplemented with a protease inhibitor cocktail (Servicebio) to extract total protein. Subsequently, western blotting was performed using the monoclonal rabbit GAL7 antibody (Abcam), polyclonal rabbit β-actin antibody (Servicebio), and a secondary antibody (1:5,000, Servicebio) to detect the respective proteins. The protein blot analysis was repeated three times using the same method.

Immunohistochemistry (IHC) and analysis

To assess GAL7 expression in cervical HSIL and cervical cancer tissues, we performed IHC on paraffin sections of mouse cervical cancer xenografts (n = 5 per cell line, 3 cell lines: SiHa, HeLa, C-33 A, totaling 15 cases) and paraffin sections of cervical pathology from patients at Nanfang Hospital of Southern Medical University (n = 10 per group, 3 groups: HSIL, squamous cell carcinoma, adenocarcinoma, totaling 30 cases). For IHC staining, a monoclonal rabbit GAL7 antibody (Abcam) was used. Subsequently, the samples were imaged using a slide scanner (Pannoramic MIDI II, 3DHISTECH), and the IHC Profiler plugin in Image J software was utilized for automated scoring. The average gray value (indicative of staining intensity) and the percentage of positively stained area (indicative of staining extent) were employed as the IHC measurement parameters [39, 40]. Based on pathological evaluation criteria, these parameters resulted in four scoring categories: strong positive 3+ (high positive, gray value 0–60), positive 2+ (positive, gray value 61–120), weak positive 1+ (low positive, gray value 121–180), and negative 0 (negative, gray value 181–236). The IHC scores were subsequently reviewed by experienced pathologists.

Synthesis and characterization of GAL7-FITC and IgG2a-FITC

Firstly, anti-Gal7 antibody (0.2 mg/mL, 150 µL, Proteintech) or IgG2a (9.7 mg/mL, 120 µL, Bioxcell) was dissolved in 1 mL of dimethyl sulfoxide (DMSO, Solarbio). Next, 3 mg of triethylamine (30 µM) was added to the solution. The reaction was carried out in darkness at 25 ℃ for 12 h. After that, the solution was dialyzed in ultrapure water for 24 h using a dialysis bag with a molecular weight cutoff above 1000. The resulting filtrate was stored at -80 ℃ for 6 h, freeze-dried, and obtained as separate yellow powders: 2.8 µg GAL7-FITC and 1 mg IgG2a-FITC. These reagents were stored in the dark at -20 ℃. In the experiment, the powders were dissolved in phosphate-buffered saline (PBS, Omacgene) to prepare series concentrations. The absorption spectra was then acquired using a UV-Vis spectrophotometer (UV-3600 Plus, SHIMADZU, Japan), and fluorescence emission was obtained using a FluoroMax-4 spectrofluorometer (Horiba Scientific).

To minimize the interference caused by non-specific fluorescence, a fluorescent reagent called IgG2a-FITC was synthesized as a control in this experiment. Unlike GAL7-FITC, the fluorescence produced by IgG2a-FITC is unrelated to the presence of specific antigen molecules on the cell surface. IgG2a-FITC is a non-specific imaging probe, where IgG2a is conjugated with the FITC fluorescent dye. It shares the same isotype as the anti-GAL7 antibody.

Cellular uptake of GAL7-FITC

Flow cytometry (FCM) was conducted to evaluate the cellular uptake of GAL7-FITC and IgG2a-FITC in H8, SiHa, HeLa, and C-33 A cells. Cells in logarithmic growth phase from each cell type were trypsinized, resulting in a total count of 2 × 105 cells. These cells were then treated with 200 µL of GAL7-FITC or IgG2a-FITC (both 0.8 µg/mL) for 10 min. Following two washes with PBS, the cells were resuspended in 300 µL of PBS for analysis using a flow cytometer (Cytek). For each condition, three replicates were prepared.

Fluorescence microscopy imaging and subcellular localization

The GAL7-FITC or IgG2a-FITC localization in H8, SiHa, HeLa, and C-33 A cells was detected using a triple-fluorescent staining method. The cells were digested with trypsin and seeded in a 6-well plate (Corning) with circular cover glass placed at the bottom of each well at a density of 1.2 × 106 cells. After 24 h incubation in a cell culture incubator, the cells were fixed with cell fixation solution (Solarbio) for 15 min to prepare cell smears. The primary antibodies, mitochondrial marker (TOMM20, 1:5000, Servicebio) and lysosomal marker (LAMP2, 1:5000, Servicebio), were added and incubated overnight, followed by incubation with secondary antibody HRP-conjugated goat anti-rabbit IgG (1:500, Servicebio) at 25℃ for 50 min. Then, the corresponding types of TSA-CY3-Tyramide (1:500, Servicebio) and CY5/iF488-Tyramide (1:500, Servicebio) were added and incubated for 10 min. Finally, GAL7-FITC or IgG2a-FITC (both 0.8 µg/mL) was added and set for 1 h. After staining the cell nucleus with DAPI (Servicebio), the cells were mounted with an anti-fading mounting medium (Servicebio). The images were acquired using an upright fluorescence microscope (Nikon). Scanning and photography were performed using a scanner (Pannoramic MIDI II, 3DHISTECH). The cell nucleus was stained blue, the GAL7-FITC or IgG2a-FITC channel was green, the mitochondrial CY3 channel was red, and the lysosomal CY5 channel was pink.

In vitro cell toxicity assay

SiHa, HeLa, C-33 A, and H8 cells in the logarithmic growth phase were placed in a 96-well plate. Each well contained 5 × 103 cells and 100 µL of complete culture medium. After 24 h of incubation, the culture medium was replaced with 100 µL of complete culture medium containing different concentrations of GAL7-FITC (0.4, 0.8, 1.6, 3.2, 6.4 µg/mL). There were 5 replicate wells for each concentration. The plate was left incubating overnight. The next day, the culture medium was removed and replaced with 100 µL of complete culture medium containing 10 µL of CCK-8 reagent. The plate was incubated in a CO2 incubator for 1 h. The absorbance at 450 nm was measured using a multi-mode microplate reader (Synergy HT; BioTek) to determine the optical density (OD) value. To calculate cell viability, the OD value of the control wells needed to reach 1.5. The relative cell viability was calculated using the following formula: Relative cell viability (%) = (OD experimental group - OD blank group) / (OD control group - OD blank group) × 100.

Ex vivo fluorescence imaging

Ex vivo fluorescence imaging was conducted using staining techniques on detached tissues. For fluorescence imaging of mouse tumors and HSIL tissues stained with GAL7-FITC or IgG2a-FITC, we employed the IVIS Spectrum small animal live optical 3D imaging system (Caliper Life Sciences) and Cellvizio imaging (fiber optic live confocal fluorescence microscope, Mauna Kea Technologies), respectively. The concentration of GAL7-FITC or IgG2a-FITC used was 0.8 µg/mL, showing consistent fluorescence intensity. It allowed us to assess the effectiveness of GAL7-FITC in cervical lesion screening. Figure 1a provides an overview of the animal experiment process.

Our experimental subjects comprised 3 groups: (1) SiHa, HeLa, or C33-A xenograft tumor group (n = 3/cell line); (2) HSIL cervical group (n = 6); (3) SiHa cervical squamous carcinoma in-situ group (n = 3). The organs or tumor tissues from each group were divided into two parts and stained with GAL7-FITC or IgG2a-FITC (both 0.8 µg/mL), respectively. After a 5 min staining, the tissues were thoroughly washed with PBS for 5 min. Images were acquired using the IVIS imaging system, and the fluorescence intensity of each group was analyzed. We compared the difference in mean fluorescence intensity (MFI) within each group after staining with GAL7-FITC or IgG2a-FITC. Additionally, the Cellvizio system with 488 nm excitation light and a 0.3 mm microscope was used to capture the dynamic process of cell fluorescence imaging in tumor tissue. From each group, we selected three representative images, which were then converted to grayscale values using Image J software. The inter-group difference of MFI was statistically analyzed for each image.

Fluorescence imaging of cervical cone biopsy tissue in patients

To facilitate the clinical application of GAL7-FITC, a clinical imaging experiment was conducted using post-cone biopsy specimens (Fig. 1b, ethical approval number: NFEC-2022-486). Initially, the patient’s cervical biopsy indicated the presence of cervical intraepithelial neoplasia (CIN) III. Subsequently, a cone biopsy procedure was performed on the patient’s cervix. The fresh ex vivo cervical tissue obtained from the procedure was gently rinsed with PBS and subsequently stained with GAL7-FITC (0.8 µg/mL). The staining process was carried out at 25 ℃ for a duration of 3 min. Following the staining, the specimen was rinsed with PBS for an additional 5 min to remove any excess dye. For clinical imaging purposes, a customized imaging system (DPM-ENDOSCOPE-0130, PF03 and HX5800, Zhuhai Dipu Medical Technology Co., Ltd.) was utilized. This system’s FITC fluorescence module employs a 488 nm excitation laser and a 520 nm emission filter to specifically detect GAL7-FITC signals, with a sensitivity threshold of ≤ 1 nM and 12-bit dynamic range for high-resolution imaging. The integrated NIR module (778 nm excitation / 795 emission) was inactive in this study. The imaging procedure involved capturing both white light and fluorescence images of the specimen. After the imaging session, the specimen was fixed using a 4% paraformaldehyde solution (Macgene Biotechnology). Subsequently, the specimen underwent H&E staining and GAL7 IHC (immunohistochemistry) for further analysis.

Statistical analysis

All experiments were performed with at least three independent replicates (n ≥ 3).

Data are presented as mean ± standard deviation (SD). Statistical significance was determined using unpaired two-tailed Student’s t-tests for comparisons between two groups. P-values < 0.05 were considered statistically significant. GraphPad Prism 9.0 (GraphPad Software, USA) was used for all analyses. For fluorescence intensity comparisons, raw grayscale values from ImageJ were normalized to background signals prior to statistical evaluation.

Results

GAL7 expression in CESC

We examined the GEPIA dataset and observed that the expression level of GAL7 was significantly higher in squamous cell carcinoma of the CESC than in normal tissues (*P < 0.05, Fig. 2a). Furthermore, in Fig. 2b, it is evident that GAL7 exhibited elevated expression in the SiHa, HeLa, and C-33 A cell lines as compared to the normal control H8 cell line. Specifically, the GAL7 expression in SiHa was 4.18-fold higher than that in H8 (*P = 0.0190), in HeLa it was 2.45-fold higher than H8 (*P = 0.0308), and it was 3.15-fold higher in C-33 A than H8 (*P = 0.0295).

Fig. 2.

Fig. 2

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Expression of GAL7. (a) Statistical analysis of GAL7 expression in CESC tumor and normal tissues obtained from the GEPIA database. Log2(TPM + 1) was used for the log-scale. (b) Western blotting analysis of GAL7 protein expression in various cell lines (H8, SiHa, HeLa, and C33-A). (c) & (d) Representative GAL7 IHC and H&E histology obtained from human and mouse xenograft cervical cancer tissues. (e) IHC scores of GAL7 expression in IHC samples. Scale bar of overview, 200 μm. Scale bar of cancer and normal, 50 μm. * P < 0.05, ** P < 0.01, **** P < 0.0001. CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; HSIL, high-grade squamous cell carcinoma; SCC, squamous intraepithelial lesion; AC, adenocarcinoma

For the analysis and verification of GAL7 protein distribution, we employed the GAL7 antibody to conduct H&E and IHC staining on paraffin sections of human HSIL, squamous cell carcinoma (SCC), and adenocarcinoma (AC) patient samples (Fig. 2c). Similarly, GAL7 IHC staining was performed on xenograft mouse tumors as shown in Fig. 2d. The results revealed distinct GAL7 expression patterns, where HSIL and tumor areas exhibited high GAL7 expression, while adjacent normal tissue displayed lower expression levels (Fig. 2e, *P < 0.01, ****P < 0.000). Detailed patient characteristics, pathological diagnosis, tumor staging, and IHC scores can be found in the SI Table 1.

Characterization of GAL7-FITC imaging probe

Spectral analysis revealed that GAL7-FITC and IgG2a-FITC (both 0.8 µg/mL), exhibited maximum absorption wavelengths at 494 nm, matching the excitation wavelength of the FITC dye. Additionally, the infrared maximum absorption wavelengths of GAL7-FITC and IgG2a-FITC solutions were found to be at 520 nm (Fig. 3a).

Fig. 3.

Fig. 3

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Characterization and uptake of GAL7-FITC. (a) Absorption and fluorescence emission spectra of of GAL7-FITC and IgG2a-FITC. (b) FACS of H8, SiHa, HeLa, and C-33 A cells stained with GAL7-FITC. (c) FACS MFI of different cell lines. (d) Cell viabiliaty of different cell lines (SiHa, HeLa, C-33, and H8) stained with different concentrations of GAL7-FITC. * P < 0.05, ** P < 0.01

To further investigate the cellular binding ability, GAL7-FITC and IgG2a-FITC were incubated with the cells and analyzed using flow cytometry (Fig. 3b). The mean fluorescence intensity (MFI) of GAL7-FITC was consistently higher than that of the control IgG2a-FITC in all four cell lines (Fig. 3c, * P < 0.05, ** P < 0.01). The MFI values and statistical details are provided in SI Table 2. Moreover, the MFI of C-33 A was significantly higher than that of H8. These findings suggest that GAL7-FITC exhibits superior cellular binding to tumor tissues compared to the non-targeted control, demonstrating effective targeting within CESC.

Furthermore, it was observed that when GAL7-FITC was present at the working concentration (0.8 µg/mL), the average cell viability for all cell lines remained above 85% (Fig. 3d). This indicates that GAL7-FITC does not adversely affect the viability and activity of cells and tissues in vitro. Therefore, the utilization of GAL7-FITC ensures the subsequent experiments and guarantees the accuracy of the obtained results. We performed a thorough in vivo safety assessment of GAL7-FITC to examine its systemic toxicity and biocompatibility(SI Fig. 2). The results affirm that GAL7-FITC shows no acute systemic toxicity at the tested dose, corroborating its potential for translational applications.

Subcellular localization of GAL7-FITC in fluorescence microscopy imaging

Upon incubation with GAL7-FITC (Fig. 4), cervical cancer cells exhibited a more pronounced GAL7-FITC fluorescence signal (green) than H8 cells. The fluorescence intensity of squamous cell carcinoma cells SiHa and C-33 A surpassed that of adenocarcinoma cells HeLa, aligning with the findings from our western blot experiments. Within tumor cells, GAL7-FITC fluorescence signal colocalized with the lysosome signal (pink), indicating its subcellular localization within the lysosomes, as expected based on GAL7 protein expression.

Fig. 4.

Fig. 4

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Fluorescence microscopic imaging and subcellular localization of GAL7-FITC in different cell lines (H8, SiHa, C-33 A and HeLa). Lysosomes were stained with LAMP2 (pink). Mitochondria were stained with TOMM20 (red). Nuclei were stained with DAPI (blue). Scale bar, 50 μm

Ex vivo fluorescence imaging of GAL7-FITC

The mouse xenograft tumors (SiHa, HeLa, and C33-A), cervical HSIL, and cervical squamous cell carcinoma tissue specimens were divided into two parts. These specimens were then sprayed with GAL7-FITC or IgG2a-FITC. The imaging process was carried out using the IVIS Spectrum apparatus (Fig. 5a). The fluorescence intensities of GAL7-FITC and IgG2a-FITC were found to be almost equal (Fig. 5b). It is noteworthy that GAL7-FITC exhibited a significantly higher fluorescence intensity compared to IgG2a-FITC (Fig. 5c). This suggests that GAL7-FITC has a high specific binding affinity for HSIL and cervical tumor lesions.

Fig. 5.

Fig. 5

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Fluorescence molecular imaging (FMI) of cervical cancer and HSIL tissue stained with GAL7-FITC. (a) FMI of ex vivo xenograft tumors (SiHa, HeLa, and C33-A), HSIL and in-situ squamous cervical carcinoma of mice. (b) Fluorescence intensity of GAL7-FITC and IgG2a-FITC. (c) Analysis of MFI of cervical cancer and HSIL tissue stained with GAL7-FITC. * P < 0.05, ** P < 0.01, *** P < 0.001

Subsequently, we utilized Cellvizio for ex vivo pCLE imaging of the aforementioned mouse models (Fig. 6a). The cellular fluorescence intensity of GAL7-FITC (green) was found to be significantly higher than that of IgG2a-FITC (Fig. 6b, * P < 0.05). These results further validate the efficacy of GAL7-FITC fluorescence imaging in detecting cervical lesions. Upon removing the squamous cell (SiHa) tumor that had been stained with GAL7-FITC from the mouse cervix. These sections were then subjected to H&E staining and imaged using a fluorescence microscope (Fig. 6c). Notably, GAL7-FITC fluorescence signals (green) were observed in abnormal, precancerous cells. This observation demonstrates the accurate and rapid targeting capability of GAL7-FITC specifically in these areas.

Fig. 6.

Fig. 6

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Specific binding of GAL7-FITC in HSIL biospecimens of mice and human patients. (a) Ex vivo CLE of tumor xenografts and HSIL of mice stained with GAL7-FITC. (b) CLE MFI analysis of tumor and HSIL. (c) Fluorescence microscopy scans of in-situ cervical SiHa squamous carcinoma stained with GAL7-FITC. (d) Fluorescence imaging (FI) of GAL7-FITC staining, H&E histology and GAL7 IHC staining of fresh HSIL biospecimens from a patient. Red lines indicate the area of cervical lesions. MFI: mean fluorescence intensity

Based on the aforementioned preclinical investigations, we proceeded to perform a translational exploratory trial utilizing GAL7-FITC on freshly acquired cervical HSIL patient biopsies. The HSIL lesions were not discernible in the conventional white light images. Nonetheless, subsequent application of GAL7-FITC staining for a duration of 3 min yielded a distinct fluorescent signal within the HSIL region, with the absence of such signal in the adjacent normal tissue. The validity of this observation was further supported by histological H&E and GAL7 IHC staining of the biopsies (Fig. 6d).

Discussion

Early detection and timely treatment greatly improve the prognosis of cervical cancer. Clinical cervical screening typically involves the use of acetic acid and iodine, guided biopsy of the cervical lesion area under electronic colposcopy. However, this method relies on operators’ subjectivity, and its inability to provide real-time visual examination of cervical tissue histology can result in unnecessary invasive biopsies. These procedures unavoidably impose mental and physical stress on patients. Therefore, the development of a strategy allowing real-time molecular imaging and rapid diagnosis of cervical tissue would be of great clinical significance.

Our study identifies GAL7 as a potential biomarker for cervical cancer and HSIL imaging. Bioinformatics analysis demonstrated significant overexpression of GAL7 in cervical squamous cell carcinoma compared to normal tissues. Immunohistochemical staining of mouse and human biospecimens indicated high GAL7 expression in HSIL, cervical glandular carcinoma, and squamous carcinoma areas compared to adjacent normal tissues, validating its potential as a cervical screening biomarker. Quantification of GAL7 through immunohistochemical staining and protein imprinting further supports its use in targeting cervical lesions during clinical colposcopy. In our study, we developed a novel targeted fluorescent probe, GAL7-FITC, by conjugating anti-GAL7 antibody with FITC fluorescent dye. This is the first report demonstrating the efficacy of a GAL7-targeted imaging probe specifically for HSIL detection. The probe was rigorously validated through various preclinical models, including human and mouse tumor cells, subcutaneous tumor models, and orthotopic animal models, all yielding promising results. To assess the clinical applicability, we further tested the probe on human tissue samples through spraying application, successfully proving its feasibility.

Our experimental approach included UV-visible absorption and infrared spectra analysis, flow cytometry, and fluorescence microscopy imaging were performed to validate the successful construction of GAL7-FITC imaging probe. The probe consistently showed higher fluorescence intensity in cervical cancer cells compared to normal cervical epithelial cells. These findings endorse the reliability of GAL7 as a critical target for cervical lesion imaging. Moreover, we conducted clinical imaging by staining fresh cervical biopsies from HSIL patients with GAL7-FITC, detecting clear fluorescence signals in the HSIL region. This suggests the potential for GAL7-FITC to enable rapid and accurate identification of cervical lesions during colposcopic examinations, ultimately aiding clinical decision-making and patient care.

We compared the performance of GAL7-FITC to conventional colposcopy techniques (e.g., acetic acid/iodine staining) and surgeon-guided biopsy protocols. Unlike these methods, which rely heavily on subjective visual interpretation or intraoperative experience, GAL7-FITC enables real-time, operator-independent detection of abnormalities with molecular specificity. This eliminates the need for extensive training and reduces variability in lesion identification, particularly in low-resource settings where access to specialized expertise is limited. Furthermore, GAL7-FITC demonstrates superior specificity compared to traditional histopathology workflows, which often require time-consuming tissue processing and expert analysis. By providing immediate diagnostic feedback, GAL7-FITC enhances both accuracy and efficiency in cervical lesion management, enabling timely interventions that may improve patient outcomes.

The reduction of unnecessary biopsies not only underscores significant ethical benefits by minimizing invasive procedures and patient discomfort but also offers considerable cost savings through shorter diagnostic timelines [41–42]. Despite the promising results, several aspects warrant further exploration before clinical implementation. The safety profile of GAL7-FITC needs thorough assessment to rule out potential adverse reactions or false positives for future clinical applications. Large-scale, multi-center clinical trials are essential to confirm its specificity, sensitivity, and overall diagnostic accuracy across diverse patients’ populations. Furthermore, integrating GAL7-FITC staining into existing diagnostic workflows should be carefully evaluated for cost-effectiveness, usability, and compatibility with current clinical practices. We speculate on the potential role of GAL7 in other types of squamous carcinomas, such as skin or gastrointestinal neoplasms [43–45], and propose that GAL7-FITC could serve as a versatile platform technology for the detection of these malignancies. This broadens the implications of our work, positioning it as a foundational step toward wider applications in oncology.

Conclusion

In summary, we identified GAL7 as a potential target for cervical lesion. Our developed fluorescent probe GAL7-FITC can effectively target cervical intraepithelial lesions within a short time period on different animal tumor models and also clinical biopsies. The fluorescence signal is easily detected with standard equipment, allowing for quick and accurate identification of suspicious lesions. This facilitates precise colposcopic biopsies and suggests strong clinical translation potential. This study introduces a promising approach for cervical cancer diagnostics with significant translational value, potentially improving cervical cancer screening and management.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1 (3.6MB, tif)
Supplementary Material 2 (9.1MB, tif)
Supplementary Material 3 (16.3KB, docx)
Supplementary Material 4 (11.8KB, docx)
Supplementary Material 5 (21MB, tif)

Acknowledgements

Not applicable.

Authors’ contributions

(I) Primary research and study coordination: X.T. and C.T. (II) Data analysis and interpretation: K.H.; (III) Study design and methodology oversight: C.C.; (IV) Project supervision, strategic planning, and resource acquisition: J.T.; (V) Manuscript preparation, editing, and critical revisions: Y.D.; (VI) Final approval of manuscript: All authors.

Funding

This study was supported by the Fujian Province Natural Science Foundation of China (2024J08310), Fujian provincial health technology project (2024GGB28). Xiamen health high quality development science and technology project (2024GZL-GG48). National Natural Science Foundation of China (No. U24A20731, 82272111, 92159303, 62027901). The National Key R&D Program of China 2023YFC3402804 and SQ2024AAA030653. Beijing Natural National Science Foundation (No. 7252292). Shaanxi Fundamental Science Research Project for Chemistry and Biology (22JHQ088). Science and Technology Innovation 2030 (2023ZD0501700).

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The experiments were conducted in accordance with the Medical Ethics committee of NanFang Hospital of Southem Medical University (protocol code NFEC-2022-486, 2022-11-30).

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Xiaohui Teng and Chu Tang contributed equally to this work.

Contributor Information

Chunlin Chen, Email: ccl1@smu.edu.cn.

Jie Tian, Email: jie.tian@ia.ac.cn.

Yang Du, Email: yang.du@ia.ac.cn.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Material 1 (3.6MB, tif)
Supplementary Material 2 (9.1MB, tif)
Supplementary Material 3 (16.3KB, docx)
Supplementary Material 4 (11.8KB, docx)
Supplementary Material 5 (21MB, tif)

Data Availability Statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Articles from EJNMMI Research are provided here courtesy of Springer-Verlag

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