In Vivo Fluorescence Imaging of Gastrointestinal Stromal Tumors Using Fluorophore-Conjugated Anti-KIT Antibody
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Gastrointestinal stromal tumors (GISTs) are frequently characterized by KIT overexpression. Tumor-free margins and complete cytoreduction of disease are mainstays of treatment. We hypothesized that fluorescently labeled anti-KIT antibodies can label GIST in vivo.
KIT K641E+/− transgenic mice that spontaneously develop cecal GISTs were used in this study, with C57BL/6 mice serving as controls. Alexa 488 fluorophore-conjugated anti-KIT antibodies were delivered via the tail vein 24 h prior to fluorescence imaging. Following fluorescence laparoscopy, mice were sacrificed. The gastrointestinal tracts were grossly examined for tumors followed by fluorescence imaging. Tumors were harvested for histologic confirmation.
KIT K641E+/− mice and C57BL/6 control mice received anti-KIT antibody or isotope control antibody. Fluorescence laparoscopy had a high tumor signal-to-background noise ratio. Upon blinded review of intravital fluorescence and bright light images, there were 2 false-positive and 0 false-negative results. The accuracy was 92 %. The sensitivity, specificity, positive and negative predictive values were 100, 87, 85, and 100 %, respectively, for the combined modalities.
In this study, we present a method for in vivo fluorescence labeling of GIST in a murine model. Several translatable applications include: laparoscopic staging; visualization of peritoneal metastases; assessment of margin status; endoscopic differentiation of GISTs from other benign submucosal tumors; and longitudinal surveillance of disease response. This novel approach has clear clinical applications that warrant further research and development.
KeywordsImatinib Gastrointestinal Stromal Tumor Peritoneal Metastasis Laparoscopic Staging Metastatic Gist
The authors thank Dr. Jurg Rohrer (BD Pharmingen) for providing anti-KIT and isotype control antibodies. This work was supported in part by the National Cancer Institute CA142669 and CA132971 (to Dr. Bouvet and AntiCancer Inc.), as well as T32CA121938 (to Dr. Metildi).
Dr. Sicklick is a consultant to Novartis Pharmaceuticals. Dr. Hoffman is a non-salaried president and a stockholder in AntiCancer Inc. The remaining authors have no relevant financial disclosures.
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- 7.Chourmouzi D, Sinakos E, Papalavrentios L, Akriviadis E, Drevelegas A. Gastrointestinal stromal tumors: a pictorial review. Gastrointestin Liver Dis. 2009;18:379–83.Google Scholar
- 10.Park S, Ryu MH, Ryoo BY, et al. The role of surgical resection following imatinib treatment in patients with metastatic or recurrent GIST. J Clin Oncol. 2012;30(Suppl):abstract 62.Google Scholar
- 13.Metildi CA, Kaushal S, Lee C, et al. An LED light source and novel fluorophore combinations improve fluorescence laparoscopic detection of metastatic pancreatic cancer in orthotopic mouse models. J Am Coll Surg. 2012;214:997–1007.e1002.Google Scholar