GLUT1 as a generic biomarker enables near-infrared fluorescence molecular imaging guided precise intraoperative tumor detection in breast cancer

IF 8.6 1区 医学 Q1 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING European Journal of Nuclear Medicine and Molecular Imaging Pub Date : 2025-01-21 DOI:10.1007/s00259-025-07095-4
Si-Qi Qiu, Xiao-Feng He, Xiao-Long Liang, Guang-Yuan Shi, Meng-Long Zhao, Fan Li, Zhi-Yong Wu, Jie Tian, Tian-Tian Zhai, Yang Du
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Abstract

Purpose

Precise tumor excision is important but challenging in breast-conserving surgery (BCS). Tumor-specific fluorescence imaging may be used for intraoperative tumor detection and, therefore, to guide precise tumor excision. The aims of this study are to develop a glucose transporter 1 (GLUT1)-targeted near-infrared fluorescence tracer and evaluate its accuracy for breast cancer detection using fresh surgical breast specimens.

Methods

Bioinformatic analysis was performed to compare GLUT1 expression between breast cancer and normal breast tissues. A GLUT1-targeted fluorescence imaging tracer WZB117-CY7.5 was developed. In combination with fluorescence imaging (FMI), its binding specificity to GLUT1 was examined in in vitro breast cancer cell experiments, in vivo 4T1 breast tumor-bearing mouse models, and 60 freshly resected human breast tumor tissues. The diagnostic accuracy of WZB117-CY7.5, was evaluated in fresh specimens derived from 60 patients diagnosed with breast cancer.

Results

GLUT1 expression is higher in breast cancer tissues compared with normal tissues. WZB117-CY7.5 specifically bound to breast cancer cells in in vitro cell experiments and accumulated in tumor areas in a 4T1 tumor-bearing mice after intravenous injection by FMI. Moreover, WZB117-CY7.5 specifically bound to freshly resected human breast cancer and demonstrated excellent diagnostic performance in discriminating breast cancer, irrespective of cancer subtype, from normal breast tissue on fresh surgically resected breast tissues.

Conclusions

WZB117-CY7.5 showed high accuracy in intraoperative breast cancer detection, irrespective of the cancer subtype. This highlights its potential for clinical applications as a generic tracer for fluorescence image-guided surgery (FIGS) in BCS and fluorescence image-guided pathology for tissue sampling.

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作为通用生物标记物,GLUT1 可实现近红外荧光分子成像引导的乳腺癌术中肿瘤精确检测
目的在保乳手术中,肿瘤的精确切除是重要的,但也是一个挑战。肿瘤特异性荧光成像可用于术中肿瘤检测,从而指导精确的肿瘤切除。本研究的目的是开发一种葡萄糖转运蛋白1 (GLUT1)靶向的近红外荧光示踪剂,并评估其在使用新鲜乳房手术标本检测乳腺癌中的准确性。方法采用生物信息学方法比较GLUT1在乳腺癌组织和正常乳腺组织中的表达。研制了glut1靶向荧光成像示踪剂WZB117-CY7.5。结合荧光成像(FMI)技术,在体外乳腺癌细胞实验、体内4T1乳腺荷瘤小鼠模型和60例刚切除的人乳腺肿瘤组织中检测其对GLUT1的结合特异性。在60例乳腺癌患者的新鲜标本中评估WZB117-CY7.5的诊断准确性。结果glut1在乳腺癌组织中的表达高于正常组织。体外细胞实验中,WZB117-CY7.5与乳腺癌细胞特异性结合,经FMI静脉注射后在4T1荷瘤小鼠肿瘤区域积累。此外,WZB117-CY7.5与新鲜切除的人乳腺癌特异性结合,在手术切除的新鲜乳腺组织中对正常乳腺组织和不同癌症亚型的乳腺癌具有良好的诊断效果。结论swzb117 - cy7.5在手术中对不同癌症亚型的乳腺癌检测具有较高的准确率。这突出了它作为一种通用示踪剂在BCS中荧光图像引导手术(FIGS)和荧光图像引导病理组织采样的临床应用潜力。
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来源期刊
CiteScore
15.60
自引率
9.90%
发文量
392
审稿时长
3 months
期刊介绍: The European Journal of Nuclear Medicine and Molecular Imaging serves as a platform for the exchange of clinical and scientific information within nuclear medicine and related professions. It welcomes international submissions from professionals involved in the functional, metabolic, and molecular investigation of diseases. The journal's coverage spans physics, dosimetry, radiation biology, radiochemistry, and pharmacy, providing high-quality peer review by experts in the field. Known for highly cited and downloaded articles, it ensures global visibility for research work and is part of the EJNMMI journal family.
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