Non-Small Cell Lung Cancer Imaging Using a Phospholipase A2 Activatable Fluorophore

Area of Science:

• Biomedical optics
• Molecular imaging
• Surgical oncology

Background:

• Lung cancer necessitates improved intraoperative detection methods for accurate surgical margin evaluation.
• Current techniques struggle to identify microscopic residual disease, impacting patient outcomes.

Purpose of the Study:

• To evaluate DDAO-arachidonate (DDAO-A), a phospholipase A2 (PLA2)-activatable fluorophore, for real-time optical identification of lung cancer during surgery.
• To assess DDAO-A's stability, specificity, and efficacy in preclinical and ex vivo models.

Main Methods:

• DDAO-A was formulated in liposomes and tested for fluorescence activation by PLA2 enzymes.
• Stability studies were conducted under various storage conditions.
• Cell-based assays and in vivo mouse models were used to assess DDAO-A activation and specificity.
• Ex vivo topical application on human and canine lung cancer tissues was performed.

Main Results:

• DDAO-A demonstrated optimal characteristics in 100 nm extruded EggPC liposomes and showed excellent stability.
• Cell studies confirmed DDAO-A activation was proportional to lung cancer cell number.
• DDAO-A exhibited preferential activation by cPLA2 compared to a control probe (DDAO-P).
• Ex vivo studies showed preferential DDAO-A activation in tumor tissue with tumor-to-normal ratios up to 5.2:1.

Conclusions:

• DDAO-A is a promising fluorophore for intraoperative lung cancer detection and margin assessment.
• Its stability, specificity, and ability to highlight tumor tissue suggest potential for improving surgical precision.
• DDAO-A may enhance curative resection rates by aiding in the identification of residual disease.