Evaluation of optical imaging agents in a fluorescence-guided surgical model of head and neck cancer

Surg Oncol. 2018 Jun;27(2):225-230. doi: 10.1016/j.suronc.2018.04.004. Epub 2018 Apr 26.

Abstract

Background: Tumor proliferation often occurs from pathologic receptor upregulation. These receptors provide unique targets for near-infrared (NIR) probes that have fluorescence-guided surgery (FGS) applications. We demonstrate the use of three smart-targeted probes in a model of head and neck squamous cell carcinoma.

Methods: A dose escalation study was performed using IntegriSense750, ProSense750EX, and ProSense750FAST in mice (n = 5) bearing luciferase-positive SCC-1 flank xenograft tumors. Whole body fluorescence imaging was performed serially after intravenous injection using commercially available open-field (LUNA, Novadaq, Canada) and closed-field NIR systems (Pearl, LI-COR, Lincoln, NE). An ex vivo, whole-body biodistribution was conducted. Lastly, FGS was performed with IntegriSense750 to demonstrate orthotopic and metastatic disease localization.

Results: Disease fluorescence delineation was assessed by tumor-to-background fluorescence ratios (TBR). Peak TBR values were 3.3 for 1 nmol ProSense750EX, 5.5 for 6 nmol ProSense750FAST, and 10.8 for 4 nmol IntegriSense750 at 5.5, 3, and 4 d post administration, respectively. Agent utility is unique: ProSense750FAST provides sufficient contrast quickly (TBR: 1.5, 3 h) while IntegriSense750 produces strong (TBR: 10.8) contrast with extended administration-to-resection time (96 h). IntegriSense750 correctly identified all diseased nodes in situ during exploratory surgeries. Ex vivo, whole-body biodistribution was assessed by tumor-to-tissue fluorescence ratios (TTR). Agents provided sufficient fluorescence contrast to discriminate disease from background, TTR>1. IntegriSense750 was most robust in neural tissue (TTR: 64) while ProSense750EX was superior localizing disease against lung tissue (TBR: 13).

Conclusion: All three agents appear effective for FGS.

Keywords: Fluorescence imaging; Head and neck cancer; Optical guided surgery; Surgical oncology.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / diagnostic imaging
  • Carcinoma, Squamous Cell / secondary
  • Carcinoma, Squamous Cell / surgery*
  • Female
  • Fluorescent Dyes*
  • Head and Neck Neoplasms / diagnostic imaging
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / surgery*
  • Humans
  • Mice
  • Mice, Nude
  • Models, Anatomic*
  • Optical Imaging / methods*
  • Surgery, Computer-Assisted / methods*
  • Tumor Cells, Cultured

Substances

  • Fluorescent Dyes