Novel PET Imaging Probe for Quantitative Detection of Senescence In Vivo.
Xin XiangChuning DongLianbo ZhouJun LiuZachary M RabinowitzYuzhao ZhangHonghui GuoFeng HeXingdou ChenYunhua WangLina CuiXiaowei MaPublished in: Journal of medicinal chemistry (2024)
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.
Keyphrases
- pet imaging
- pet ct
- positron emission tomography
- dna damage
- endothelial cells
- computed tomography
- stress induced
- living cells
- high resolution
- quantum dots
- loop mediated isothermal amplification
- photodynamic therapy
- cancer therapy
- risk assessment
- label free
- cell death
- drug delivery
- cell therapy
- oxidative stress
- dual energy
- image quality
- magnetic resonance imaging
- bone marrow