Sensitive and quantitative in vivo analysis of PD-L1 using magnetic particle imaging and imaging-guided immunotherapy
Zhengyao Peng1,2, Chang Lu3, Guangyuan Shi1,4
1CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.
Insights
This study pioneers Magnetic Particle Imaging (MPI) to monitor programmed cell death ligand-1 (PD-L1) expression, guiding immunotherapy for enhanced cancer treatment effectiveness. MPI offers sensitive, non-invasive visualization of PD-L1, improving precision medicine outcomes.
Area of Science:
- Biomedical Imaging
- Nanotechnology
- Immunotherapy
Background:
- Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) expression are crucial biomarkers for predicting immunotherapy response in cancer.
- Sensitive and non-invasive imaging of immune checkpoint biomarkers is essential for accurate detection, characterization, and image-guided immunotherapy in precision medicine.
- Magnetic Particle Imaging (MPI) is an emerging modality with high sensitivity, no depth limitation, positive contrast, and no radiation, making it suitable for monitoring biomarkers.
Purpose of the Study:
- To investigate the use of MPI for monitoring PD-L1 expression.
- To develop and utilize MPI-guided immunotherapy for enhanced cancer treatment.
- To establish a novel imaging strategy for optimizing immunotherapy management.
Main Methods:
- Development of anti-PD-L1 antibody (aPDL1)-conjugated magnetic fluorescent hybrid nanoparticles (MFNPs-aPDL1).
- Dynamic monitoring and quantification of PD-L1 expression in tumors using MPI and fluorescence imaging (FMI).
- Validation of in vivo imaging results using ex vivo qPCR, western blotting, and immunofluorescence staining.
- Application of MPI for guiding PD-L1 immunotherapy.
Main Results:
- MPI and FMI successfully monitored and quantified PD-L1 expression with high sensitivity and specificity.
- Ex vivo analyses confirmed the accuracy of the in vivo imaging observations.
- MPI-guided PD-L1 immunotherapy demonstrated enhanced effectiveness in cancer treatment.
Conclusions:
- This is the first study to use MPI with MFNPs-aPDL1 probes for dynamic visualization and quantification of PD-L1 expression.
- The developed imaging strategy shows potential for clinical optimization of immunotherapy management.
- MPI offers a promising non-invasive tool for monitoring PD-L1 and guiding cancer immunotherapy.
Purpose:
The programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) expression correlate with the immunotherapeutic response rate. The sensitive and non-invasive imaging of immune checkpoint biomarkers is favorable for the accurate detection and characterization, image-guided immunotherapy in cancer precision medicine. Magnetic particle imaging (MPI), as a novel and emerging imaging modality, possesses the advantages of high sensitivity, no image depth limitation, positive contrast, and absence of radiation. Hence, in this study, we performed the pioneer investigation of monitoring PD-L1 expression using MPI and the MPI-guided immunotherapy.
Methods:
We developed anti-PD-L1 antibody (aPDL1)-conjugated magnetic fluorescent hybrid nanoparticles (MFNPs-aPDL1) and utilized MPI in combination with fluorescence imaging (FMI) to dynamically monitor and quantify PD-L1 expression in various tumors with different PD-L1 expression levels. The ex vivo real-time polymerase chain reaction (qPCR), western blotting, and immunofluorescence staining analysis were further performed to validate the in vivo imaging observation. Moreover, the MPI was further performed for the guidance of immunotherapy.
Results:
Our data showed that PD-L1 expression can be specifically and sensitively monitored and quantified using MPI and FMI imaging methods, which were validated by ex vivo qPCR and western blotting analysis. In addition, MPI-guided PD-L1 immunotherapy can enhance the effectiveness of cancer immunotherapy.
Conclusion:
To our best knowledge, this is the pioneer study to utilize MPI in combination with a newly developed MFNPs-aPDL1 imaging probe to dynamically visualize and quantify PD-L1 expression in tumor microenvironment. This imaging strategy may facilitate the clinical optimization of immunotherapy management.
