Novel PET Imaging Probe for Quantitative Detection of Senescence In Vivo.

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 [68Ga]Ga-BGal was obtained with a high labeling yield (90.0 ± 4.3%) and a radiochemical purity (>95%). [68Ga]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 [68Ga]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 [68Ga]Ga-BGal. This finding holds the potential for translating senescence imaging into clinical applications.

细胞衰老的实时检测在临床上仍然是一个挑战。在此，我们旨在开发一种正电子发射断层扫描（PET）成像探针，其靶向衰老相关β - 半乳糖苷酶（SA - β - Gal）——细胞衰老最广泛使用的生物标志物，并研究其对细胞衰老进行实时体内定量检测的性能。获得了一种稳定的PET显像剂[68Ga]Ga - BGal，其标记产率高（90.0 ± 4.3%），放射化学纯度（>95%）。[68Ga]Ga - BGal在体外和体内对β - Gal均显示出高灵敏度和特异性。探针的反应和摄取与β - Gal浓度及反应时间相关。在PET成像中，高表达β - Gal的CT26.CL25肿瘤和经多柔比星处理的HeLa肿瘤显示出来自[68Ga]Ga - BGal的高信号，而在CT26.WT和未处理的HeLa肿瘤中观察到低信号。总之，我们展示了使用探针[68Ga]Ga - BGal在临床前模型中对衰老进行成功的PET成像。这一发现为将衰老成像转化为临床应用提供了可能。