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AUNP-12 Near-Infrared Fluorescence Probes across NIR-I to NIR-II Enable In Vivo Detection of PD-1/PD-L1 Axis in the
Xinyu Zhang1, Ping Wang2, Guangyuan Shi3
1Department 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.
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.
Insights
New molecular imaging probes, AUNP-12-Cy5.5 and AUNP-12-CH1055, enable noninvasive visualization of programmed cell death protein 1 ligand 1 (PD-L1) expression. This facilitates precise patient selection for immunotherapy and dynamic monitoring of treatment response.
Area of Science:
- Oncology
- Molecular Imaging
- Immunotherapy
Background:
- Programmed cell death protein 1 (PD-1)/PD-L1 pathway inhibitors show variable efficacy (20-40%) in cancer treatment.
- Risk of hyperprogression after immunotherapy necessitates improved patient selection strategies.
- Molecular imaging offers noninvasive, real-time visualization of dynamic PD-L1 expression in vivo.
Purpose of the Study:
- To develop novel near-infrared (NIR) fluorescence imaging probes for PD-L1.
- To evaluate the efficacy of these probes in mapping PD-L1 expression in preclinical cancer models.
- To explore the potential of these probes for guiding clinical immunotherapy.
Main Methods:
- Conjugation of a novel PD-L1-targeting peptide antagonist (AUNP-12) with Cy5.5 and CH1055 dyes.
- Utilizing AUNP-12-Cy5.5 for first NIR (NIR-I) and AUNP-12-CH1055 for second NIR (NIR-II) imaging.
- Testing probe efficacy in various mouse tumor models to visualize PD-L1 expression.
Main Results:
- AUNP-12-Cy5.5 and AUNP-12-CH1055 effectively mapped PD-L1 expression in vivo across different tumor models.
- The probes provided insights into tumor-immune interactions.
- Demonstrated feasibility of NIR fluorescence imaging for PD-L1 visualization.
Conclusions:
- AUNP-12-based probes offer a promising approach for molecular imaging of PD-L1.
- These probes can aid in precise patient stratification for immunotherapy.
- Potential for dynamic monitoring supports personalized cancer care strategies.
