Design, Synthesis, and Biological Evaluation of a Small-Molecule PET Agent for Imaging PD-L1 Expression

Area of Science:

• Radiochemistry
• Molecular Imaging
• Oncology

Background:

• Immunotherapy targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway offers therapeutic benefits but has suboptimal response rates.
• PD-L1 expression in tumors correlates with treatment response and survival, necessitating accurate measurement for patient selection.
• Non-invasive methods for assessing PD-L1 expression are crucial for optimizing cancer immunotherapy.

Purpose of the Study:

• To design and synthesize a novel small molecular positron emission tomography (PET) probe, [18F]LP-F, for quantifying PD-L1 expression in tumors.
• To evaluate the radiochemical properties, stability, and binding affinity of the [18F]LP-F probe.
• To assess the in vivo specificity and tumor uptake of [18F]LP-F using micro-PET imaging.

Main Methods:

• Synthesis and radiolabeling of the [18F]LP-F PET probe.
• Assessment of radiochemical yield, purity, molar activity, and stability in vitro.
• In vitro binding assays to determine affinity for PD-L1.
• In vivo micro-PET imaging in tumor-bearing mouse models to evaluate biodistribution and tumor accumulation.

Main Results:

• The [18F]LP-F probe was successfully synthesized with a radiochemical yield of 12.72 ± 1.98%, high purity (>98%), and good molar activity (18.8 GBq/μmol).
• [18F]LP-F demonstrated good stability in PBS and mouse serum, with moderate in vitro affinity for PD-L1.
• Micro-PET imaging revealed significantly higher tumor accumulation of [18F]LP-F in A375-hPD-L1 tumors compared to A375 tumors, indicating specific binding to PD-L1.

Conclusions:

• The novel PET probe [18F]LP-F can be effectively synthesized and exhibits favorable characteristics for PET imaging.
• [18F]LP-F demonstrates specific binding to PD-L1, as evidenced by differential tumor uptake in vivo.
• This probe holds potential for non-invasive assessment of PD-L1 expression, aiding in patient selection for PD-1/PD-L1 targeted immunotherapies.