Imaging of primary and metastatic pancreatic cancer using a fluorophore-conjugated anti-CA19-9 antibody for surgical navigation.
BACKGROUND
Despite recent surgical advances, pancreatic cancer remains the fourth leading cause of cancer-related death in the United States. This is due to inaccurate staging and difficulty in achieving negative margins at the time of pancreaticoduodenectomy. CA19-9 is a carbohydrate tumor-associated antigen found in up to 94% of pancreatic adenocarcinomas. In this study we investigate the use of a fluorophore-labeled anti-CA19-9 monoclonal antibody to improve intraoperative visualization of both primary and metastatic tumors in a mouse model of pancreatic cancer.


METHODS
A monoclonal antibody specific for CA19-9 was conjugated to a green fluorophore and delivered to tumor-bearing mice as a single intravenous (IV) dose. Intravital fluorescence imaging was used to localize tumor implants 24 h after antibody administration.


RESULTS
Using fluorescence imaging, the primary tumor was clearly visible at laparotomy, as were small metastatic implants within the liver and spleen and on the peritoneum. These tumor implants, which were nearly impossible to see using standard bright-field imaging, demonstrated clear fluorescence under LED light excitation. The fluorescence signal within the tumor tissue was maintained for over 3 weeks after a single administration of the labeled antibody. Histologic evaluation of tissue from animals treated with the conjugated anti-CA19-9 antibody likewise revealed strong staining of the tumor cells with minimal background staining of the peritumoral stroma.


CONCLUSIONS
Fluorophore-labeled anti-CA19-9 offers a novel intraoperative imaging technique for enhanced visualization of primary and metastatic tumors in pancreatic cancer when CA19-9 expression is present and may improve intraoperative staging and efficacy of resection.
McElroy
Michele
M
Department of Surgery, University of California, San Diego, California 92093, USA.
Kaushal
Sharmeela
S
Luiken
George A
GA
Talamini
Mark A
MA
Moossa
A R
AR
Hoffman
Robert M
RM
Bouvet
Michael
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D018395:CA-19-9 Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D013160:Splenic Neoplasms / Q000175:diagnosis* / Q000556:secondary; D013238:Stereotaxic Techniques
D000911:Antibodies, Monoclonal; D018395:CA-19-9 Antigen