Preclinical antibody-PET imaging of PD-L1

Area of Science:

• Oncology
• Immunotherapy
• Radiochemistry

Background:

• Immune checkpoint inhibitors targeting Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) have revolutionized cancer therapy.
• Accurate patient selection for PD-1/PD-L1 blockade remains a challenge due to limitations of biopsy-based diagnostics in capturing tumor heterogeneity.
• Current methods fail to fully predict response, as some PD-L1-negative tumors benefit from immunotherapy, while some PD-L1-positive tumors do not.

Purpose of the Study:

• To review recent advancements in PD-1/PD-L1 targeted positron emission tomography (PET) imaging for cancer immunotherapy.
• To highlight the expansion of preclinical models and novel anti-PD-L1 antibodies/fragments for immunoPET development.
• To discuss the utility of these tools in assessing the spatial and temporal heterogeneity of PD-L1 expression.

Main Methods:

• Review of PD-1/PD-L1 targeted immunoPET studies published in the last four years.
• Focus on preclinical tumor models and the development of anti-PD-L1 antibodies and antibody fragments for PET imaging.
• Analysis of how these imaging agents and models can address PD-L1 expression heterogeneity.

Main Results:

• The development and application of zirconium-89 labeled anti-PD-L1 antibodies have enabled in vivo visualization of PD-L1 expression.
• Expansion of preclinical models and antibody-based targeting agents for PD-L1 immunoPET.
• Demonstration of immunoPET's potential to assess real-time, whole-tumor PD-L1 heterogeneity.

Conclusions:

• PD-1/PD-L1 targeted immunoPET offers a promising strategy for non-invasive assessment of PD-L1 expression and heterogeneity.
• This technology has the potential to improve patient selection for immune checkpoint inhibitor therapy.
• Further development of preclinical models and imaging agents will enhance the clinical utility of PD-L1 immunoPET.