Novel PET Imaging Probe for Quantitative Detection of Senescence In Vivo

  • J Med Chem. 2024 Mar 20. doi: 10.1021/acs.jmedchem.4c00179.
Xin Xiang  1 ,  Chuning Dong  1 ,  Lianbo Zhou  1 ,  Jun Liu  2 ,  Zachary M Rabinowitz  2 ,  Yuzhao Zhang  2 ,  Honghui Guo  1 ,  Feng He  1 ,  Xingdou Chen  1 ,  Yunhua Wang  1 ,  Lina Cui  2 ,  Xiaowei Ma  1
Affiliations
  • 1. Department of Nuclear Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
  • 2. Department of Medicinal Chemistry, College of Pharmacy, UF Health Science Center, University of Florida, Gainesville, Florida 32610, United States.
PMID: 38507820 DOI: 10.1021/acs.jmedchem.4c00179
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 [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.

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