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Updated: Jul 13, 2025
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
A bifunctional agent for efficient imaging of PD-L1 and antimelanoma activity
Jin Wang1, Xiaoyan Pan1, Ping Hai2
1School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, China.
Abstract:
Immune checkpoint inhibitors targeting PD-L1 lead to challenging patterns of efficacy and toxicity. Herein, by focusing on tracing the molecular biomarker of response to efficacy, we formulated a central hypothesis for the construction of theranostic functional monoclonal antibody incorporation with tracing ability based on fluorescence turn-on and controllable release strategies. Functional atezolizumab was constructed by in situ assembly of both biorthogonal group and controllable release group. The theranostic monoclonal antibodies achieved quantitative monitoring of PD-L1 on cells with different expression levels through biorthogonal light-up fluorescence, followed by the release of atezolizumab in combination with high tumor reduction conditions to promote immune activation. The combination of bio-orthogonal reaction-driven fluorescence turn-on and tumor microenvironment-responsive controllable release afforded theranostic bifunctional monoclonal antibodies for the detection of PD-L1 and combination therapy. Remarkably, these novel theranostics might be used as probes for fluorescent imaging and simultaneously achieving potent antitumor efficacy.
Insights
This study developed a novel theranostic antibody that tracks programmed death-ligand 1 (PD-L1) using fluorescence and releases atezolizumab for enhanced cancer immunotherapy. This dual-action approach improves efficacy and monitoring of PD-L1 targeted treatments.
Area of Science:
- Immunology and Cancer Therapeutics
- Bioconjugation and Theranostics
Background:
- Immune checkpoint inhibitors targeting PD-L1 show variable efficacy and toxicity.
- Accurate monitoring of PD-L1 expression is crucial for predicting treatment response.
- Development of theranostic agents combining diagnostic and therapeutic functions is needed.
Purpose of the Study:
- To construct a functional monoclonal antibody with integrated tracing and therapeutic capabilities.
- To develop a theranostic antibody for quantitative monitoring of PD-L1 expression.
- To achieve controllable drug release for enhanced immune activation and antitumor efficacy.
Main Methods:
- Engineered atezolizumab by incorporating biorthogonal and controllable release groups.
- Utilized biorthogonal light-up fluorescence for quantitative PD-L1 monitoring.
- Implemented tumor microenvironment-responsive release of atezolizumab for combination therapy.
Main Results:
- Successfully constructed theranostic monoclonal antibodies capable of quantitative PD-L1 detection.
- Demonstrated fluorescence turn-on for monitoring PD-L1 on cells with varying expression levels.
- Achieved potent antitumor efficacy through controlled atezolizumab release, promoting immune activation.
Conclusions:
- Developed novel theranostic bifunctional monoclonal antibodies for PD-L1 detection and combination therapy.
- The combination of fluorescence turn-on and responsive drug release offers a dual approach for cancer treatment.
- These theranostics show potential as fluorescent imaging probes with simultaneous potent antitumor efficacy.
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