Imaging-guided companion diagnostics in radiotherapy by monitoring APE1 activity with afterglow and MRI imaging

Renye Yue, Zhe Li, Huiyi Liu, Youjuan Wang, Yuhang Li, Rui Yin, Baoli Yin, Haisheng Qian, Heemin Kang, Xiaobing Zhang and Guosheng Song ()
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Renye Yue: Hunan University
Zhe Li: Hunan University
Huiyi Liu: Hunan University
Youjuan Wang: Hunan University
Yuhang Li: Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University)
Rui Yin: Hunan University
Baoli Yin: Hunan University
Haisheng Qian: Anhui Medical University
Heemin Kang: Korea University
Xiaobing Zhang: Hunan University
Guosheng Song: Hunan University

Nature Communications, 2024, vol. 15, issue 1, 1-23

Abstract: Abstract Companion diagnostics using biomarkers have gained prominence in guiding radiotherapy. However, biopsy-based techniques fail to account for real-time variations in target response and tumor heterogeneity. Herein, we design an activated afterglow/MRI probe as a companion diagnostics tool for dynamically assessing biomarker apurinic/apyrimidinic endonuclease 1(APE1) during radiotherapy in vivo. We employ ultrabright afterglow nanoparticles and ultrasmall FeMnOx nanoparticles as dual contrast agents, significantly broadening signal change range and enhancing the sensitivity of APE1 imaging (limit of detection: 0.0092 U/mL in afterglow imaging and 0.16 U/mL in MRI). We devise longitudinally and transversely subtraction-enhanced imaging (L&T-SEI) strategy to markedly enhance MRI contrast and signal-to-noise ratio between tumor and normal tissue of living female mice. The combined afterglow and MRI facilitate both anatomical and functional imaging of APE1 activity. This probe enables correlation of afterglow and MRI signals with APE1 expression, radiation dosage, intratumor ROS, and DNA damage, enabling early prediction of radiotherapy outcomes (as early as 3 h), significantly preceding tumor size reduction (6 days). By monitoring APE1 levels, this probe allows for early and sensitive detection of liver organ injury, outperforming histopathological analysis. Furthermore, MRI evaluates APE1 expression in radiation-induced abscopal effects provides insights into underlying mechanisms, and supports the development of treatment protocols.

Date: 2024
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DOI: 10.1038/s41467-024-50688-0

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