Intraoperative Molecular Imaging of Lung Adenocarcinoma Can Identify Residual Tumor Cells at the Surgical Margins

Mol Imaging Biol. 2016 Apr;18(2):209-18. doi: 10.1007/s11307-015-0878-9.

Abstract

Purpose: During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection.

Procedures: Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in three humans with lung adenocarcinoma.

Results: The peak tumor-to-background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 h and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30% of mice with positive margins. Molecular imaging identified an additional 50% of residual tumor deposits (p < 0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5.

Conclusions: Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection.

Keywords: Folate receptor alpha; Lung cancer; Molecular imaging; Surgical oncology; Thoracic surgery.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / diagnostic imaging*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery*
  • Adenocarcinoma of Lung
  • Aged
  • Animals
  • Cell Line, Tumor
  • Female
  • Fluorescent Dyes / metabolism
  • Fluorescent Dyes / pharmacokinetics
  • Folate Receptors, GPI-Anchored
  • Humans
  • Intraoperative Care*
  • Lung / pathology
  • Lung / surgery
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery*
  • Margins of Excision*
  • Mice
  • Mice, SCID
  • Middle Aged
  • Molecular Imaging / methods*
  • Neoplasm, Residual / diagnostic imaging*
  • Neoplasm, Residual / pathology*
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

Substances

  • Fluorescent Dyes
  • Folate Receptors, GPI-Anchored