Related Experiment Video
Updated: Jun 18, 2026
Harnessing the Bioorthogonal Inverse Electron Demand Diels-Alder Cycloaddition for Pretargeted PET Imaging
Published on: February 3, 2015
Bioorthogonal Diels-Alder Click Chemistry-Based Pretargeted PET Imaging Strategy for Monitoring Programmed
Yong Huang1, Zhongjing Li1, Chengze Li1
1Department of Nuclear Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, China.
This study introduces a pretargeted positron emission tomography (PET) imaging strategy using Diels-Alder click chemistry to overcome limitations in monitoring programmed cell death ligand 1 (PD-L1) expression. The developed atezolizumab-based approach enables clear visualization of PD-L1 positive tumors for improved immunotherapy selection.
Area of Science:
- Nuclear Medicine
- Oncology
- Immunotherapy
Background:
- Antibody tracers for PET imaging allow in vivo monitoring of programmed cell death ligand 1 (PD-L1) expression to guide immunotherapy.
- Slow antibody pharmacokinetics limit the use of short-lived radionuclides for PET imaging of PD-L1.
Purpose of the Study:
- To develop and evaluate a pretargeted PET imaging strategy using Diels-Alder (IEDDA) click chemistry to overcome pharmacokinetic limitations.
- To compare atezolizumab and durvalumab for pretargeted PET imaging of PD-L1 expression.
Main Methods:
- Developed a pretargeted PET imaging strategy using IEDDA click chemistry with TCO-functionalized atezolizumab/durvalumab and fluorine-18-labeled tetrazines ([18F]Tz, [18F]PEG6-Tz, [18F]PEG12-Tz).
- Tested the strategy in biodistribution and PET imaging studies using A549-PDL1 xenografts.
Main Results:
- Atezolizumab-TCO/[18F]PEG12-Tz showed suitability for pretargeted PET imaging, with optimal delineation at 48 hours post-injection.
- Achieved a tumor-to-muscle ratio of 5.33 for atezolizumab-TCO/[18F]PEG12-Tz, outperforming durvalumab-based and mock controls.
- Demonstrated clear visualization of PD-L1 positive tumors with high contrast.
Conclusions:
- Successfully established a pretargeted 18F-immuno-PET imaging technology based on atezolizumab.
- The pretargeting strategy with short-lived fluorine-18 is viable for identifying tumors with high PD-L1 expression.
- This strategy holds potential for clinical translation in selecting immunotherapy responders.
