In vivo fluorescence imaging of gastrointestinal stromal tumors using fluorophore-conjugated anti-KIT antibody.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Division of Surgical Oncology, Department of Surgery, University of California, San Diego, CA, USA.
Cristina A
CA
Metildi
Chih-Min
CM
Tang
Sharmeela
S
Kaushal
Stephanie Y
SY
Leonard
Paolo
P
Magistri
Hop S
HS
Tran Cao
Robert M
RM
Hoffman
Michael
M
Bouvet
Jason K
JK
Sicklick
D000818:Animals; D000911:Antibodies, Monoclonal; D004195:Disease Models, Animal; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D010535:Laparoscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; D019009:Proto-Oncogene Proteins c-kit