An LED light source and novel fluorophore combinations improve fluorescence laparoscopic detection of metastatic pancreatic cancer in orthotopic mouse models

Cristina A. Metildi, Sharmeela Kaushal, Claudia Lee, Chanae R. Hardamon, Cynthia S. Snyder, George A. Luiken, Mark A. Talamini, Robert M. Hoffman, Michael Bouvet

Research output: Contribution to journalArticle

Abstract

Background: The aim of this study was to improve fluorescence laparoscopy of pancreatic cancer in an orthotopic mouse model with the use of a light-emitting diode (LED) light source and optimal fluorophore combinations. Study Design: Human pancreatic cancer models were established with fluorescent FG-RFP, MiaPaca2-GFP, BxPC-3-RFP, and BxPC-3 cancer cells implanted in 6-week-old female athymic mice. Two weeks postimplantation, diagnostic laparoscopy was performed with a Stryker L9000 LED light source or a Stryker X8000 xenon light source 24 hours after tail-vein injection of CEA antibodies conjugated with Alexa 488 or Alexa 555. Cancer lesions were detected and localized under each light mode. Intravital images were also obtained with the OV-100 Olympus and Maestro CRI Small Animal Imaging Systems, serving as a positive control. Tumors were collected for histologic analysis. Results: Fluorescence laparoscopy with a 495-nm emission filter and an LED light source enabled real-time visualization of the fluorescence-labeled tumor deposits in the peritoneal cavity. The simultaneous use of different fluorophores (Alexa 488 and Alexa 555), conjugated to antibodies, brightened the fluorescence signal, enhancing detection of submillimeter lesions without compromising background illumination. Adjustments to the LED light source permitted simultaneous detection of tumor lesions of different fluorescent colors and surrounding structures with minimal autofluorescence. Conclusions: Using an LED light source with adjustments to the red, blue, and green wavelengths, it is possible to simultaneously identify tumor metastases expressing fluorescent proteins of different wavelengths, which greatly enhanced the signal without compromising background illumination. Development of this fluorescence laparoscopy technology for clinical use can improve staging and resection of pancreatic cancer.

Original languageEnglish (US)
JournalJournal of the American College of Surgeons
Volume214
Issue number6
DOIs
StatePublished - Jun 2012
Externally publishedYes

Fingerprint

Pancreatic Neoplasms
Fluorescence
Light
Laparoscopy
Neoplasms
Lighting
Xenon
Antibodies
Peritoneal Cavity
Nude Mice
Tail
Veins
Color
Neoplasm Metastasis
Technology
Injections
Proteins

ASJC Scopus subject areas

  • Surgery

Cite this

An LED light source and novel fluorophore combinations improve fluorescence laparoscopic detection of metastatic pancreatic cancer in orthotopic mouse models. / Metildi, Cristina A.; Kaushal, Sharmeela; Lee, Claudia; Hardamon, Chanae R.; Snyder, Cynthia S.; Luiken, George A.; Talamini, Mark A.; Hoffman, Robert M.; Bouvet, Michael.

In: Journal of the American College of Surgeons, Vol. 214, No. 6, 06.2012.

Research output: Contribution to journalArticle

Metildi, Cristina A. ; Kaushal, Sharmeela ; Lee, Claudia ; Hardamon, Chanae R. ; Snyder, Cynthia S. ; Luiken, George A. ; Talamini, Mark A. ; Hoffman, Robert M. ; Bouvet, Michael. / An LED light source and novel fluorophore combinations improve fluorescence laparoscopic detection of metastatic pancreatic cancer in orthotopic mouse models. In: Journal of the American College of Surgeons. 2012 ; Vol. 214, No. 6.
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abstract = "Background: The aim of this study was to improve fluorescence laparoscopy of pancreatic cancer in an orthotopic mouse model with the use of a light-emitting diode (LED) light source and optimal fluorophore combinations. Study Design: Human pancreatic cancer models were established with fluorescent FG-RFP, MiaPaca2-GFP, BxPC-3-RFP, and BxPC-3 cancer cells implanted in 6-week-old female athymic mice. Two weeks postimplantation, diagnostic laparoscopy was performed with a Stryker L9000 LED light source or a Stryker X8000 xenon light source 24 hours after tail-vein injection of CEA antibodies conjugated with Alexa 488 or Alexa 555. Cancer lesions were detected and localized under each light mode. Intravital images were also obtained with the OV-100 Olympus and Maestro CRI Small Animal Imaging Systems, serving as a positive control. Tumors were collected for histologic analysis. Results: Fluorescence laparoscopy with a 495-nm emission filter and an LED light source enabled real-time visualization of the fluorescence-labeled tumor deposits in the peritoneal cavity. The simultaneous use of different fluorophores (Alexa 488 and Alexa 555), conjugated to antibodies, brightened the fluorescence signal, enhancing detection of submillimeter lesions without compromising background illumination. Adjustments to the LED light source permitted simultaneous detection of tumor lesions of different fluorescent colors and surrounding structures with minimal autofluorescence. Conclusions: Using an LED light source with adjustments to the red, blue, and green wavelengths, it is possible to simultaneously identify tumor metastases expressing fluorescent proteins of different wavelengths, which greatly enhanced the signal without compromising background illumination. Development of this fluorescence laparoscopy technology for clinical use can improve staging and resection of pancreatic cancer.",
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AU - Kaushal, Sharmeela

AU - Lee, Claudia

AU - Hardamon, Chanae R.

AU - Snyder, Cynthia S.

AU - Luiken, George A.

AU - Talamini, Mark A.

AU - Hoffman, Robert M.

AU - Bouvet, Michael

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