Novel PET Imaging Probe for Quantitative Detection of Senescence In Vivo
Xin Xiang, Chuning Dong, Lianbo Zhou, Jun Liu, Zachary M. Rabinowitz, Yuzhao Zhang, Honghui Guo, Feng He, X. Chen, Yunhua Wang, Lina Cui, Xiaowei Ma
Abstract
Real-time detection of cellular senescence remains a clinical challenge. Here, we aimed to develop a positron emission tomography (PET) imaging probe targeting senescence-associated β-galactosidase (SA-β-Gal), the most widely used biomarker of cellular senescence, and investigate its performance for real-time in vivo quantitative detection of cellular senescence. A stable PET imaging agent [ 68 Ga]Ga-BGal was obtained with a high labeling yield (90.0 ± 4.3%) and a radiochemical purity (>95%). [ 68 Ga]Ga-BGal displayed high sensitivity and specificity for β-Gal both in vitro and in vivo. The reaction and uptake of the probe correlated with the β-Gal concentration and reaction time. In PET imaging, high β-Gal-expressing CT26.CL25 tumors and doxorubicin-treated HeLa tumors showed high signals from [ 68 Ga]Ga-BGal, while a low signal was observed in CT26.WT and untreated HeLa tumors. In summary, we showcased successful PET imaging of senescence in preclinical models using probe [ 68 Ga]Ga-BGal. This finding holds the potential for translating senescence imaging into clinical applications.