Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression

Area of Science:

• Oncology
• Radiochemistry
• Molecular Imaging

Background:

• Immune checkpoint blockade therapy targeting programmed cell death-protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) has transformed cancer treatment.
• Limited patient response to PD-1/PD-L1 inhibitors is often due to heterogeneous PD-L1 expression, challenging accurate detection via immunohistochemistry (IHC).
• Improved methods are needed to identify patients who will benefit from immune checkpoint blockade therapy.

Purpose of the Study:

• To develop a novel positron emission tomography (PET) imaging tracer for noninvasive assessment of PD-L1 expression in tumors.
• To evaluate the efficacy of a 68Ga-labeled dextrorotary (D)-peptide antagonist ([68Ga]DPA) for detecting PD-L1-overexpressing tumors.

Main Methods:

• Design and synthesis of a 68Ga-labeled D-peptide antagonist (DPA) targeting PD-L1.
• In vivo evaluation of [68Ga]DPA in tumor-bearing mice using PET imaging.
• Assessment of tracer stability, specificity, and imaging capabilities.

Main Results:

• The [68Ga]DPA tracer demonstrated specific binding to PD-L1-overexpressing tumors in vivo.
• [68Ga]DPA exhibited favorable stability and excellent imaging performance.
• The tracer allowed for real-time, whole-body visualization of PD-L1 expression.

Conclusions:

• [68Ga]DPA-PET imaging is a promising noninvasive approach for assessing tumor PD-L1 status.
• This method has the potential to improve patient stratification for PD-1/PD-L1 blockade therapy.
• D-peptides offer advantages like proteolytic resistance and prolonged half-lives for developing PET tracers.