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Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
Development of selective ssDNA micro-probe for PD1 detection as a novel strategy for cancer imaging
Stanisław Malicki1,2, Anna Czarna3, Edyta Żyła3,4
1Laboratory of Proteolysis and Post-translational Modification of Proteins, Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, Krakow, 30-387, Poland. stanislaw.malicki@uj.edu.pl.
Abstract:
Programmed death receptor 1, PD1, modulates the function of immune cells by providing inhibitory signals and constitutes the marker of immune exhaustion. Monitoring the level of PD1 promises a useful diagnostic approach in autoimmune diseases and cancer. Here we describe the development of an ssDNA aptamer-based molecular probe capable of specific recognition of human PD1 receptor. The aptamer was selected using SELEX, its sequence was further optimized, and the affinity and specificity were determined in biochemical assays. The aptamer was converted into a fluorescent probe and its potential in molecular imaging was demonstrated in a culture of human cells overexpressing PD1 and murine pancreatic organoids / immune cells mixed co-culture model. We conclude that the provided aptamers are suitable probes for imaging of PD1 expressing immune cells even in complex cellular models and may find future utility as diagnostic tools.
Insights
Researchers developed a novel ssDNA aptamer probe to detect Programmed Death 1 (PD1), a key marker of immune exhaustion. This probe shows promise for imaging PD1-expressing cells and potential use in diagnosing autoimmune diseases and cancer.
Area of Science:
- Biotechnology
- Immunology
- Molecular Biology
Background:
- Programmed Death 1 (PD1) is crucial in regulating immune cell function and indicates immune exhaustion.
- PD1 levels are significant biomarkers for diagnosing autoimmune diseases and cancers.
Purpose of the Study:
- To develop a specific ssDNA aptamer-based molecular probe for recognizing the human PD1 receptor.
- To evaluate the aptamer probe's utility in molecular imaging of PD1-expressing cells.
Main Methods:
- Systematic Evolution of Ligands by Exponential Enrichment (SELEX) was used for aptamer selection and optimization.
- Biochemical assays determined aptamer affinity and specificity.
- Fluorescently labeled aptamers were tested in cell cultures and co-culture models.
Main Results:
- An ssDNA aptamer with high affinity and specificity for human PD1 was successfully developed.
- The aptamer probe enabled effective molecular imaging of PD1-expressing cells in complex models.
- Demonstrated potential in human cell cultures and murine pancreatic organoid co-cultures.
Conclusions:
- The developed aptamers are effective probes for imaging PD1-expressing immune cells.
- These aptamers hold potential as diagnostic tools for immune-related diseases and cancer.
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