Non-invasive PD-L1 quantification using [¹⁸F]DK222-PET imaging in cancer immunotherapy

Area of Science:

• Molecular Imaging and Cancer Therapeutics
• Immunology and Oncology Research

Background:

• Combination immunotherapies require non-invasive biomarkers to assess clinical efficacy.
• Programmed death-ligand 1 (PD-L1) is a key target in cancer immunotherapy.
• Positron emission tomography (PET) offers a non-invasive method for monitoring therapeutic targets.

Purpose of the Study:

• To investigate [18F]DK222, a novel peptide-based tracer, for imaging PD-L1 expression.
• To evaluate the relationship between PD-L1 expression and therapy-induced changes in cancer using PET.
• To assess the utility of [18F]DK222-PET in monitoring immunotherapy response and tumor heterogeneity.

Main Methods:

• Validated [18F]DK222 specificity for PD-L1 in non-small cell lung cancer (NSCLC) and urothelial carcinoma (UC) xenografts.
• Utilized PET to quantify PD-L1 changes induced by anti-programmed cell death protein-1 (PD-1) therapy in humanized mice.
• Assessed PD-L1 pharmacodynamics with [18F]DK222-PET during monotherapy and combination immunotherapy in melanoma models.

Main Results:

• [18F]DK222-PET demonstrated variable tumor uptake correlating with PD-L1 expression in NSCLC and UC models.
• Increased [18F]DK222 uptake was observed in microsatellite instability (MSI) tumors post-anti-PD-1 therapy and in combination therapy versus monotherapy.
• Combination therapy showed higher PD-L1 expression, increased CD8+/CD4+ T-cell ratios, and distinct spatial immune infiltration patterns compared to monotherapy.

Conclusions:

• [18F]DK222-PET serves as a promising non-invasive tool for monitoring immunotherapy effects on PD-L1 expression.
• The agent can detect therapy-induced changes and differentiate the impact of various immunotherapy regimens.
• PET imaging provides insights into pathological and immunological changes, aiding in treatment assessment.