A Novel Peptide-Based PD-L1 PET Tracer: Design, Synthesis, and Preclinical Imaging Validation

Area of Science:

• Nuclear Medicine
• Radiochemistry
• Oncology

Background:

• Programmed death ligand 1 (PD-L1) is a key immune checkpoint protein expressed on various tumor cells.
• Accurate assessment of PD-L1 expression is crucial for predicting response to PD-1/PD-L1 targeted immunotherapies.

Purpose of the Study:

• To develop and evaluate a novel positron emission tomography (PET) imaging probe, [18F]-AlF-Asp2-TPP-1, for noninvasive visualization of PD-L1 expression.
• To assess the feasibility of using this probe for guiding PD-L1-targeted cancer immunotherapy.

Main Methods:

• Synthesis and characterization of the novel PET probe [18F]-AlF-Asp2-TPP-1.
• In vitro and in vivo stability studies of the radiotracer.
• Dynamic PET imaging in tumor-bearing models to evaluate tracer uptake and biodistribution.

Main Results:

• The probe [18F]-AlF-Asp2-TPP-1 was synthesized with high radiochemical yield (13.7%) and purity (>95%).
• Excellent in vitro and in vivo stability was confirmed.
• Rapid tracer accumulation in tumors was observed, with significant tumor uptake at 30, 60, and 90 minutes postinjection.

Conclusions:

• [18F]-AlF-Asp2-TPP-1 demonstrates favorable characteristics as a PET imaging agent for PD-L1 expression.
• This novel probe holds potential for noninvasive monitoring of PD-L1 levels in tumors.
• It may serve as a valuable tool to guide patient selection for PD-L1-targeted immunotherapy.