Citation: Meng Zhao, Yan Chen, Chenshuo Zhang, Jianan Ding, Qiulian Mao, Yuqi Zhang, Yinjia Gao, Yongxiang Bai, Laiqing Xie, Guohua Fan, Haibin Shi. Engineering a γ-glutamyl transpeptidase-activated fluorogenic probe for quantitative visualization and imaging-guided tumor resection[J]. Chinese Chemical Letters, ;2026, 37(3): 111061. doi: 10.1016/j.cclet.2025.111061 shu

Engineering a γ-glutamyl transpeptidase-activated fluorogenic probe for quantitative visualization and imaging-guided tumor resection

Meng Zhao ^{a, b} ,
Yan Chen ^a ,
Chenshuo Zhang ^a ,
Jianan Ding ^a ,
Qiulian Mao ^a ,
Yuqi Zhang ^a ,
Yinjia Gao ^a ,
Yongxiang Bai ^a ,
Laiqing Xie ^d ,
Guohua Fan ^{c, *,} ,
Haibin Shi ^{a, *,}

a.
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, and Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, China
b.
Department of Nuclear Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, China
c.
Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
d.
Department of Ophthalmology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China

fangh22@sina.com

hbshi@suda.edu.cn

Received Date: 19 December 2024
Revised Date: 7 March 2025
Accepted Date: 9 March 2025
Available Online: 10 March 2025

Figures(6)

Quantitative visualization of pivotal biomarkers and accurate delineation of tumor lesion boundary are highly significant to assist surgeon precisely resect the tumors and reduce the risk of recurrence. Activatable fluorescent probes hold great promise for intraoperative guidance of tumor surgery with high signal-to-background ratio (SBR). Here, we report a γ-glutamyl transpeptidase (GGT)-activated fluorogenic probe Indol-Glu for quantitative visualization of GGT and fluorescence-guided tumor resection. The fluorescence of Indol-Glu was initially “off” state but was specifically activated by GGT to produce enhanced near-infrared (NIR) fluorescence (~37-fold at 741 nm). It is also accompanied by the formation of self-assemblies in the tumor microenvironment resulting in prolonged retention in tumor tissues, which was demonstrated to be able to apply for NIR imaging-guided surgical resection of GGT-overexpressed luciferase-transfected hepatocellular carcinoma (HCC/Luc) tumor. More notably, taking advantage of the ratiometric photoacoustic signal (PA₆₉₀/PA₈₀₀) characteristic of Indol-Glu under the digestion of GGT, quantitative visual assessment of GGT activities in various tumor models was achieved in living mice. We believe that this research work may offer a powerful tool for precise diagnosis and surgical resection of malignant tumors.
- Activatable fluorogenic probe,
- γ-Glutamyl transpeptidase,
- Ratiometric photoacoustic imaging,
- Quantitative visualization,
- NIR imaging-guided surgery
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