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. 2023 Mar 10:13:1070967.
doi: 10.3389/fonc.2023.1070967. eCollection 2023.

In vivo evaluation of integrin αvβ6-targeting peptide in NSCLC and brain metastasis

Di Fan  1 , Chengkai Zhang  2 , Qi Luo  3 , Baowang Li  2 , Lin Ai  1 , Deling Li  2 , Wang Jia  2
Affiliations

In vivo evaluation of integrin αvβ6-targeting peptide in NSCLC and brain metastasis

Di Fan et al. Front Oncol. .

Abstract

Introduction: Integrin αvβ6, which is upregulated in malignancies and remains absent or weak in normal tissue, is a promising target in molecular imaging therapeutics. In vivo imaging of integrin αvβ6 could therefore be valuable for early tumor detection and intraoperative guidance.

Methods: In this study, integrin αvβ6-targeting probe G2-SFLAP3 was labeled with near-infrared (NIR) dye Cy5.5 or radioisotope 68Ga. The resulting probes were evaluated in integrin αvβ6-positive A549 and αvβ6-negative H1703 xenograft mice models.

Results: The cellar uptake of G2-SFLAP3-Cy5.5 was consistent with the expression of integrin αvβ6. Both subcutaneous and brain metastatic A549 tumors could be clearly visualized by NIR fluorescent imaging of G2-SFLAP3-Cy5.5. A549 tumors demonstrated the highest G2-SFLAP3-Cy5.5 accumulation at 4h post-injection (p.i.) and remain detectable at 84h p.i. The fluorescent signal of G2-SFLAP3-Cy5.5 was significantly reduced in H1703 and A549-blocking groups. Consistently, small-animal PET imaging showed tumor-specific accumulation of 68Ga-DOTA-G2-SFLAP3.

Discussion: G2-SFLAP3 represents a promising agent for noninvasive imaging of non-small cell lung cancer (NSCLC) and brain metastases.

Keywords: NSCLC; PET; brain metastases; integrin αvβ6; near-infrared fluorescence imaging.

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Conflict of interest statement

Author QL was employed by company Guangzhou International Bio Island. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Expression of integrin αvβ6 and uptake of G2-SFLAP3-Cy5.5 in cell lines. (A) Immunofluorescence stain of integrin αvβ6 in A549 and H1703 cell lines. (B) Cell binding images of G2-SFLAP3-Cy5.5 in A549, H1703, and G2-SFLAP3-blocked A549. (C, D) The corresponding average fluorescence intensity of immunofluorescence and cell binding assay, respectively (n=3). Data were presented as mean± SD, ****p < 0.0001.
Figure 2
Figure 2
In vivo fluorescence images of G2-SFLAP3-Cy5.5 in subcutaneously A549 and H1703 xenograft models. (A) The near-infrade fluorescence images of A549 bearing mice models at different time points after injection of G2-SFLAP3-Cy5.5. (B, C) The quantitative average fluorescence intensity and tumor/muscle signal ratio at different time points (n=4). (D) Comparison of G2-SFLAP3-Cy5.5 uptake between A549 and H1703 tumors. (E) The corresponding average fluorescence intensity in A549 and H1703 tumors (n=4). Data were presented as mean± SD, **p < 0.01.
Figure 3
Figure 3
Ex vivo fluorescence images of G2-SFLAP3-Cy5.5 in A549 brain metastasis models. (A) The NIR images of G2-SFLAP3-Cy5.5 and blocking experiment for brain metastatic A549 at 2 hours post-injection. (B) Enhanced brain MRI scan for brain metastasis xenograft model. (C) HE staining of brain slices. (D) The ex vivo images of G2-SFLAP3-Cy5.5 at 2 hours post-injection through fluorescence and visible light.
Figure 4
Figure 4
Small-animal PET image of 68Ga-DOTA-G2-SFLAP3 for mice with A549, H1703, and G2-SFLAP3-blocked A549.
See this image and copyright information in PMC

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