AUNP-12 Near-Infrared Fluorescence Probes across NIR-I to NIR-II Enable In Vivo Detection of PD-1/PD-L1 Axis in the Tumor Microenvironment

  • Bioconjug Chem. 2024 Jul 17;35(7):1064-1074. doi: 10.1021/acs.bioconjchem.4c00266.
Xinyu Zhang  1 ,  Ping Wang  2 ,  Guangyuan Shi  3 ,  Chu Tang  4 ,  Huadan Xue  1
Affiliations
  • 1. Department of Radiology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China.
  • 2. Department of Cardiology, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese People's Liberation Army (PLA) General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China.
  • 3. University of Science and Technology of China, 96 Jinzhai Road, Hefei 230026, China.
  • 4. Engineering Research Center of Molecular and Neuro Imaging of Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an 710126, China.
PMID: 38980173 DOI: 10.1021/acs.bioconjchem.4c00266
Abstract

The innovative PD-1/PD-L1 pathway strategy is gaining significant traction in Cancer therapeutics. However, fluctuating response rates of 20-40% to PD-1/PD-L1 inhibitors, coupled with the risk of hyperprogression after immunotherapy, underscore the need for accurate patient selection and the identification of more beneficiaries. Molecular imaging, specifically near-infrared (NIR) fluorescence imaging, is a valuable alternative for real-time, noninvasive visualization of dynamic PD-L1 expression in vivo. This research introduces AUNP-12, a novel PD-L1-targeting peptide antagonist conjugated with Cy5.5 and CH1055 for first (NIR-I) and second near-infrared (NIR-II) imaging. These probes have proven to be effective in mapping PD-L1 expression across various mouse tumor models, offering insights into tumor-immune interactions. This study highlights the potential of AUNP-12-Cy5.5 and AUNP-12-CH1055 for guiding clinical immunotherapy through precise patient stratification and dynamic monitoring, supporting the shift toward molecular imaging for personalized Cancer care.

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