Development of Radiotracers for Imaging of the PD-1/PD-L1 Axis

Area of Science:

• Oncology
• Immunology
• Radiochemistry

Background:

• Immune checkpoint inhibitor (ICI) therapy, targeting programmed death receptor 1 (PD-1) and its ligand PD-L1, is a key cancer treatment.
• PD-L1 is a biomarker for ICI therapy decisions and monitoring, but its expression is heterogeneous and dynamic.
• Standard immunohistochemistry struggles to capture PD-L1's heterogeneity and temporal changes.

Purpose of the Study:

• To provide an overview of molecular imaging tracers for PD-1 and PD-L1.
• To summarize preclinical and clinical data for PET, SPECT, and optical imaging (OI) radiotracers.
• To discuss the advantages, disadvantages, and future directions for PD-1/PD-L1 imaging tracers.

Main Methods:

• Review of existing PET, SPECT, and OI (radio)tracers for PD-1/PD-L1 imaging.
• Summary of preclinical and clinical data for various radiotracer molecule classes.
• Analysis of advantages and disadvantages of different imaging approaches.

Main Results:

• Molecular imaging techniques (PET, SPECT) enable whole-body assessment of PD-1/PD-L1 expression, overcoming limitations of immunohistochemistry.
• Various radiotracers targeting PD-1 and PD-L1 have been developed and evaluated in preclinical and clinical settings.
• Different molecule classes of radiotracers show varying potential for imaging PD-1/PD-L1 upregulation.

Conclusions:

• PET and SPECT imaging offer superior capabilities for evaluating dynamic and heterogeneous PD-1/PD-L1 expression in cancer patients compared to standard methods.
• Existing radiotracers show promise, but further development is needed to optimize imaging of PD-1/PD-L1 status.
• Future research should focus on novel radiotracer development for improved cancer immunotherapy monitoring and treatment selection.