PD-L1-targeted dual-modal MR/NIR-II probe for imaging and image-guided surgery of non-small cell lung cancer

Abstract

Recurrence of non-small cell lung cancer remains a critical clinical challenge. Primarily due to undetectable micrometastatic lesions and incomplete tumor resection. Current preoperative imaging modalities lack sufficient resolution to identify small lesions, while intraoperative guidance relies on visual inspection or conventional fluorescence. Accurate preoperative diagnosis and precise excision of malignant tissue remain critical factors for improving patient prognosis. Considering the differential expression of PD-L1 in NSCLC and normal lung tissue, we developed a novel imaging probe (PTPGd-ICG). This probe enabled successful MRI-based tumor targeting with high contrast in tumor-bearing mice, with the experimental group showing a 2.39-fold higher signal-to-noise ratio (SNR) than the blocking group at 0.5 h post-injection. NIR-II fluorescence imaging guided tumor removal, with the probe exhibiting sustained tumor enrichment from 4-96 h post-injection and reaching a peak tumor-to-background ratio (TBR) of 8.77 at 72 h, enabling precise tumor resection in animal models. In addition, the probe exhibited significantly higher fluorescence intensity in human NSCLC tissues than in adjacent normal tissues, facilitating the assessment of positive surgical margins ex vivo. These findings demonstrate that PD-L1 is a promising imaging target for NSCLC. This strategy may enable preoperative identification of patients with high PD-L1 expression while facilitating rapid pathological assessment and intraoperative margin delineation.