Intraoperative localization of insulinoma and normal pancreas using invisible near-infrared fluorescent light

Joshua H. Winer, Hak Soo Choi, Summer L. Gibbs-Strauss, Yoshitomo Ashitate, Yolonda L. Colson, John V. Frangioni

Research output: Contribution to journalArticlepeer-review

58 Scopus citations


Background: Neuroendocrine tumors of the pancreas, such as insulinoma, are difficult to localize, and complete resection is essential for cure. Our hypothesis is that a near-infrared (NIR) fluorophore exhibiting uptake in insulinoma could provide high-sensitivity detection intraoperatively. Materials and Methods: The optical properties of methylene blue (MB) were measured in vitro in 100% serum at 37°C and in vivo after tissue uptake. MB was injected as a rapid intravenous bolus at doses ranging from 0.25 to 2 mg/kg into wildtype rats and pigs, and into insulinoma-bearing transgenic mice. The FLARE imaging system was used to acquire color video and NIR fluorescence images simultaneously and in real-time. The signal-to-background ratios (SBR) of tissues and tumors were quantified using FLARE software. Results: When appropriately diluted, MB exhibits moderate NIR fluorescence emission peaking at 688 nm. At doses ≥1 mg/kg, certain normal tissues, such as pancreas, accumulate MB and remain NIR fluorescent for up to 1 h with an SBR ≥ 1.6. MB spectral properties are maintained after uptake into tissue. Interestingly, insulinoma exhibits even higher MB signal than normal pancreas, resulting in insulinoma-to-pancreas ratios of 3.7 and insulinoma-to-muscle ratios of 16.2. MB permitted high-sensitivity, real-time localization of primary, multicentric, and metastatic insulinoma and permitted differentiation among tumor, normal pancreas, and other abdominal structures. Conclusion: A single intravenous injection of a clinically available, commonly used NIR fluorophore provides prolonged intraoperative localization of normal pancreas and insulinoma using invisible NIR fluorescent light.

Original languageEnglish (US)
Pages (from-to)1094-1100
Number of pages7
JournalAnnals of surgical oncology
Issue number4
StatePublished - Apr 2010
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Oncology


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