Multifunctional Probe Based on "Chemical Antibody-Aptamer" for Noninvasive Detection of PD-L1 Expression in Cancer

Area of Science:

• Biomedical Imaging
• Molecular Imaging
• Cancer Diagnostics

Background:

• Immune checkpoint inhibitors (ICIs) targeting programmed cell death ligand 1 (PD-L1) show promise in cancer treatment, but variable patient response necessitates accurate PD-L1 expression monitoring.
• Heterogeneity in PD-L1 expression poses a challenge for predicting and tracking ICI therapy efficacy.
• Sensitive and quantitative in vivo analysis of PD-L1 is crucial for personalized treatment strategies.

Purpose of the Study:

• To develop and evaluate an aptamer-based dual-modality positron emission tomography/near-infrared fluorescence (PET/NIRF) imaging probe for PD-L1.
• To assess the probe's specificity, sensitivity, and stability for in vitro and in vivo imaging of PD-L1.
• To demonstrate the probe's utility in monitoring dynamic changes in PD-L1 expression during cancer therapy.

Main Methods:

• Automated solid-phase oligonucleotide synthesis was used to prepare the probe precursor NOTA-Cy5-R1.
• The precursor was radiolabeled with Gallium-68 to create the PET/NIRF dual-modality probe [68Ga]Ga-NOTA-Cy5-R1.
• In vitro assessments included flow cytometry, fluorescence imaging, and cellular uptake studies. In vivo studies involved PET/NIRF imaging of tumor-bearing mice and ex vivo analyses.

Main Results:

• The synthesized [68Ga]Ga-NOTA-Cy5-R1 probe exhibited good fluorescence properties and in vitro stability.
• In vivo PET/NIRF imaging demonstrated sensitive and specific binding to PD-L1 positive tumors with a high signal-to-noise ratio due to rapid clearance from non-target tissues.
• The probe successfully monitored changes in PD-L1 expression in xenografts treated with cisplatin, correlating well with ex vivo validation.

Conclusions:

• [68Ga]Ga-NOTA-Cy5-R1 is a potent dual-modality imaging probe for visualizing PD-L1 positive tumors.
• The probe facilitates sensitive monitoring of dynamic PD-L1 expression changes, potentially aiding in guiding and optimizing immune checkpoint inhibitor therapy.
• This imaging approach holds promise for advancing clinical decision-making in cancer treatment.