Immunotherapy

Immune checkpoint inhibitors (ICIs), such as anti–PD-1 and anti–PD-L1 therapies, have transformed the treatment landscape for non–small cell lung cancer (NSCLC) and many other malignancies. However, only a subset of patients experience durable responses. The biological mechanisms underlying response, delayed response, and resistance remain incompletely understood, and robust imaging biomarkers for patient stratification and early prediction of response are lacking.

Traditional biomarkers—such as those obtained from tumor biopsies—capture only a small spatial and temporal snapshot of a highly dynamic process. Immune activation unfolds across tumors, tumor-draining lymph nodes, and systemic lymphoid organs, with substantial heterogeneity within and between patients.

Our Approach

We are conducting a longitudinal study in NSCLC patients receiving anti–PD-(L)1 therapy using total-body dynamic [¹⁸F]F-AraG PET imaging. Each participant undergoes:

• A baseline scan prior to therapy
• An early post-treatment scan (~2 weeks after initiation of therapy)
• A later scan near the standard-of-care radiographic response evaluation (~12 weeks)

Total-body PET offers exceptional sensitivity for simultaneous imaging of:

• Primary tumors and metastases
• Peritumoral margins
• Tumor-draining lymph nodes
• Major lymphoid organs (spleen, bone marrow)
• Other organs potentially involved in systemic immune modulation

This study design allows us to move beyond the tumor imaging and capture both early immune activation and later dynamics associated with lymphocyte trafficking, response, or resistance. Rather than relying on static uptake measures alone, we perform compartmental kinetic modeling to quantify T cell activation and vascular perfusion parameters. Lastly, in collaboration with Dr. Tianhong Li's lab at UC Davis, we will look into correlations with peripheral immune biomarkers using multicolor flow cytometry and cytokine profiling.

Broader Impact

While this pilot study focuses on NSCLC, the framework we are developing is broadly applicable to:

• Other solid tumors treated with ICIs
• Combination immunotherapy strategies
• Monitoring immune-related adverse events
• Early-phase immunomodulatory drug development

Our long-term goal is to establish quantitative total-body immune imaging as a biomarker platform for precision immuno-oncology.

Funding:

UC Davis EXPLORER Pilot Program, UC Davis School of Medicine

MPI: N Omidvari, T Li