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

Michael C Hart1, Ritesh K Isuri1,2, Drew Ramos1

  • 1Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.

Chemical & Biomedical Imaging
|July 26, 2024
PubMed
Summary
This summary is machine-generated.

A novel fluorescent probe, DDAO-arachidonate (DDAO-A), shows promise for real-time lung cancer detection during surgery. This tool aids in identifying cancerous tissue, potentially improving surgical outcomes and resection rates.

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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.