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

Abstract

The development of immune checkpoint blockade therapy based on programmed cell death-protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) has revolutionized cancer therapies in recent years. However, only a fraction of patients responds to PD-1/PD-L1 inhibitors, owing to the heterogeneous expression of PD-L1 in tumor cells. This heterogeneity presents a challenge in the precise detection of tumor cells by the commonly used immunohistochemistry (IHC) approach. This situation calls for better methods to stratify patients who will benefit from immune checkpoint blockade therapy, to improve treatment efficacy. Positron emission tomography (PET) enables real-time visualization of the whole-body PD-L1 expression in a noninvasive way. Therefore, there is a need for the development of radiolabeled tracers to detect PD-L1 distribution in tumors through PET imaging. Compared to their L-counterparts, dextrorotary (D)-peptides have properties such as proteolytic resistance and remarkably prolonged metabolic half-lives. This study designed a new method to detect PD-L1 expression based on PET imaging of 68Ga-labeled PD-L1-targeted D-peptide, a D-dodecapeptide antagonist (DPA), in tumor-bearing mice. The results showed that the [68Ga]DPA can specifically bind to PD-L1-overexpressing tumors in vivo, and showed favorable stability as well as excellent imaging ability, suggesting that [68Ga]DPA-PET is a promising approach for the assessment of PD-L1 status in tumors.

• Authors: Lulu Zhang, Siqi Zhang, Wenyu Wu, Xingkai Wang, Jieting Shen, Dongyuan Wang, Kuan Hu, Ming-Rong Zhang, Feng Wang, Rui Wang
• Journal: Journal of visualized experiments : JoVE (J Vis Exp) Issue 192 (02 03 2023) ISSN: 1940-087X [Electronic] United States
• PMID: 36806629 (Publication Type: Journal Article, Video-Audio Media, Research Support, Non-U.S. Gov't)

Chemical References

• CD274 protein, human
• B7-H1 Antigen
• Programmed Cell Death 1 Receptor
• Gallium Radioisotopes
• Immune Checkpoint Inhibitors
• Peptides

Topics

• Mice
• Animals
• B7-H1 Antigen (metabolism)
• Programmed Cell Death 1 Receptor (metabolism)
• Gallium Radioisotopes (chemistry)
• Immune Checkpoint Inhibitors
• Positron-Emission Tomography (methods)
• Neoplasms
• Peptides (chemistry)