Fluorophore-conjugated anti-CEA Antibody for the Intraoperative Imaging of Pancreatic and Colorectal Cancer

被引:124
作者
Kaushal, Sharmeela [1 ]
McElroy, Michele K. [1 ]
Luiken, George A. [2 ]
Talamini, Mark A. [1 ]
Moossa, A. R. [1 ]
Hoffman, Robert M. [1 ,3 ]
Bouvet, Michael [1 ]
机构
[1] Univ Calif San Diego, Moores Canc Ctr, Dept Surg, La Jolla, CA 92093 USA
[2] OncoFluor Inc, San Diego, CA USA
[3] AntiCanc Inc, San Diego, CA USA
关键词
Pancreatic neoplasms; Colorectal neoplasms; Carcinoembryonic antigen; Fluorescent antibody technique; Nude mouse cancer models; Fluorescence-guided surgery;
D O I
10.1007/s11605-008-0581-0
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Introduction Colorectal and pancreatic cancers together comprise the third and fourth most common causes of cancer-related death in the United States. In both of these cancers, complete detection of primary and metastatic lesions at the time of surgery is critical to optimal surgical resection and appropriate patient treatment. Materials and Methods We have investigated the use of fluorophore-labeled anti-carcinoembryonic antigen (CEA) monoclonal antibody to aid in cancer visualization in nude mouse models of human colorectal and pancreatic cancer. Anti-CEA was conjugated with a green fluorophore. Subcutaneous, orthotopic primary and metastatic human pancreatic and colorectal tumors were easily visualized with fluorescence imaging after administration of conjugated anti-CEA. The fluorescence signal was detectable 30 min after systemic antibody delivery and remained present for 2 weeks, with minimal in vivo photobleaching after exposure to standard operating room lighting. Tumor resection techniques revealed improved ability to resect labeled tumor tissue under fluorescence guidance. Comparison of two different fluorophores revealed differences in dose-response and photobleaching in vivo. Conclusion These results indicate that fluorophore-labeled anti-CEA offers a novel intraoperative imaging technique for enhanced visualization of tumors in colorectal and pancreatic cancer when CEA expression is present, and that the choice of fluorophore significantly affects the signal intensity in the labeled tumor.
引用
收藏
页码:1938 / 1950
页数:13
相关论文
共 39 条
[31]   Detection and clinical significance of occult tumour cells in colorectal cancer [J].
Tsavellas, G ;
Patel, H ;
Allen-Mersh, TG .
BRITISH JOURNAL OF SURGERY, 2001, 88 (10) :1307-1320
[32]   Strategies for the treatment of synchronous liver metastasis [J].
Turrini, O. ;
Viret, F. ;
Guiramand, J. ;
Lelong, B. ;
Bege, T. ;
Delpero, J. R. .
EJSO, 2007, 33 (06) :735-740
[33]   Curative resection is the single most important factor determing outcome in patients with pancreatic adenocarcinoma [J].
Wagner, M ;
Redaelli, C ;
Lietz, M ;
Seiler, CA ;
Friess, H ;
Büchler, MW .
BRITISH JOURNAL OF SURGERY, 2004, 91 (05) :586-594
[34]   Assessment of bevacizumab conjugated to Cy5.5 for detection of head and neck cancer xenografts [J].
Withrow, Kirk P. ;
Newman, J. Robert ;
Skipper, Joni B. ;
Gleysteen, John P. ;
Magnuson, J. Scott ;
Zinn, Kurt ;
Rosenthal, Eben L. .
TECHNOLOGY IN CANCER RESEARCH & TREATMENT, 2008, 7 (01) :61-66
[35]   Surgery for pancreatic cancer: Recent controversies and current practice [J].
Wray, CJ ;
Ahmad, SA ;
Matthews, JB ;
Lowy, AM .
GASTROENTEROLOGY, 2005, 128 (06) :1626-1641
[36]   PANCREATICODUODENAL CARCINOMA - A CLINICOPATHOLOGICAL STUDY OF 304 PATIENTS AND IMMUNOHISTOCHEMICAL OBSERVATION FOR CEA AND CA19-9 [J].
YAMAGUCHI, K ;
ENJOJI, M ;
TSUNEYOSHI, M .
JOURNAL OF SURGICAL ONCOLOGY, 1991, 47 (03) :148-154
[37]   Development of real-time subcellular dynamic multicolor imaging of cancer-cell trafficking in live mice with a variable-magnification whole-mouse imaging system [J].
Yamauchi, K ;
Yang, M ;
Jiang, P ;
Xu, MX ;
Yamamoto, N ;
Tsuchiya, H ;
Tomita, K ;
Moossa, AR ;
Bouvet, M ;
Hoffman, RM .
CANCER RESEARCH, 2006, 66 (08) :4208-4214
[38]   Facile whole-body imaging of internal fluorescent tumors in mice with an LED flashlight [J].
Yang, M ;
Luiken, G ;
Baranov, E ;
Hoffman, RM .
BIOTECHNIQUES, 2005, 39 (02) :170-+
[39]   Improved preoperative tumor staging by 5-aminolevulinic acid induced fluorescence laparoscopy [J].
Zöpf, T ;
Schneider, ARJ ;
Weickert, U ;
Riemann, JF ;
Arnold, JC .
GASTROINTESTINAL ENDOSCOPY, 2005, 62 (05) :763-767