Tumor-Specific Fluorescence Antibody Imaging Enables Accurate Staging Laparoscopy in an Orthotopic Model of Pancreatic Cancer

Cao, Hop S. Tran; Kaushal, Sharmeela; Metildi, Cristina; Menen, Rhiana; Lee, Claudia; Snyder, Cynthia S.; Messer, Karen; Pu, Minya; Luiken, George A.; Talamini, Mark A.; Hoffman, Robert M.; Bouvet, Michael

doi:10.5754/hge11836

Cited by 41 publications

(45 citation statements)

References 22 publications

(26 reference statements)

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“…25–28 Furthermore, there has been interest in using fluorophore-conjugated antibodies to unique surface markers expressed by individual tumor types. 12,14, 29,30 These methods have all shown promising capabilities to label tumor for enhanced detection and subsequent resection under fluorescence-guidance, leading to improved DFS and OS in mouse models of cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, fluorophore-conjugated anti-CEA antibodies improved the accuracy and diagnostic yield of staging laparoscopy in orthotopic and carcinomatosis mouse models of pancreatic cancer. 14 …”

Section: Discussionmentioning

confidence: 99%

“…The antibody was labeled with the AlexaFluor 488 or 555 Protein Labeling Kit (Molecular Probes Inc., Eugene, OR) according to the manufacturer's instructions. 12–14 Antibody and dye concentrations in the final sample were quantified using spectrophotometric absorbance with a Nanodrop ND 1000 spectrophotometer.…”

Section: Methodsmentioning

confidence: 99%

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Fluorescence-guided Surgery with a Fluorophore-conjugated Antibody to Carcinoembryonic Antigen (CEA), that Highlights the Tumor, Improves Surgical Resection and Increases Survival in Orthotopic Mouse Models of Human Pancreatic Cancer

Metildi

Kaushal²,

Pu³

et al. 2014

Ann Surg Oncol

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Background We have developed a method of distinguishing normal tissue from pancreatic cancer in vivo using fluorophore-conjugated antibody to carcinoembryonic antigen (CEA). The objective of this study was to evaluate whether fluorescence-guided surgery (FGS) with a fluorophore-conjugated antibody to CEA, to highlight the tumor, can improve surgical resection and increase disease free survival (DFS) and overall survival (OS) in orthotopic mouse models of human pancreatic cancer. Methods We established nude-mouse models of human pancreatic cancer with surgical orthotopic implantation of the human BxPC-3 pancreatic cancer. Orthotopic tumors were allowed to develop for 2 weeks. Mice then underwent bright-light surgery (BLS) or FGS 24 h after intravenous injection of anti-CEA-Alexa Fluor 488. Completeness of resection was assessed from postoperative imaging. Mice were followed postoperatively until premorbid to determine DFS and OS. Results Complete resection was achieved in 92 % of mice in the FGS group compared to 45.5 % in the BLS group (p = 0.001). FGS resulted in a smaller postoperative tumor burden (p = 0.01). Cure rates with FGS compared to BLS improved from 4.5 to 40 %, respectively (p = 0.01), and 1-year postoperative survival rates increased from 0 % with BLS to 28 % with FGS (p = 0.01). Median DFS increased from 5 weeks with BLS to 11 weeks with FGS (p = 0.0003). Median OS increased from 13.5 weeks with BLS to 22 weeks with FGS (p = 0.001). Conclusions FGS resulted in greater cure rates and longer DFS and OS using a fluorophore-conjugated anti-CEA antibody. FGS has potential to improve the surgical treatment of pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Fluorescence-guided Surgery with a Fluorophore-conjugated Antibody to Carcinoembryonic Antigen (CEA), that Highlights the Tumor, Improves Surgical Resection and Increases Survival in Orthotopic Mouse Models of Human Pancreatic Cancer

Metildi

Kaushal²,

Pu³

et al. 2014

Ann Surg Oncol

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“…In addition to MN-14, other anti-CEA mAbs also have been used in preclinical studies. For example, a green fluorophore-labeled anti-CEA antibody was shown to improve tumor detection and resection in open laparotomies in mouse models (24,25), and recurrence rates were significantly decreased in mice after fluorescence-guided surgery (26).…”

Section: Discussionmentioning

confidence: 99%

SPECT- and Fluorescence Image–Guided Surgery Using a Dual-Labeled Carcinoembryonic Antigen–Targeting Antibody

et al. 2014

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“…Our laboratory has shown in mouse models, that tumorspecific fluorescence labeling of tumors allows identification of even sub-millimeter lesions in laparoscopy (13). We have developed an orthotopic colon-cancer liver metastasis model and have shown improved outcomes after resection using fluorescence labeling (14).…”

mentioning

confidence: 99%

Regarding the applications of fusion-fluorescence imaging using indocyanine green in laparoscopic hepatectomy

Lwin

Hoffman

Bouvet

2017

Transl. Gastroenterol. Hepatol.

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A critical concern in performing hepatectomy for tumor resection is determining the boundaries of resection and identifying any additional lesions. Obtaining negative margins has a direct impact on disease-free survival in patients (1). The main goal is to remove neoplastic tissue while sparing sufficient normal parenchyma and preserving organ function. Deciding the location of margins in resection for liver neoplasms is based on the location of tumor. Crosssectional imaging modalities localize the lesion and assist in pre-operative planning, but once in the operating room, the surgeon must rely on visual inspection and tactile feedback along with anatomic knowledge to localize and resect the tumor. In the setting of laparoscopic surgery, this becomes limited as bimanual palpation is no longer possible and tactile feedback becomes limited. This becomes even more so in the setting of robotic surgery as tactile feedback is absent and the surgeon must rely only on visual cues.The use of near-infrared (NIR) fluorescence imaging technology in the operating room has greatly advanced real time intra-operative imaging and target identification. Indocyanine green (ICG), a dye traditionally used for fundoscopy and estimations of cardiac and hepatic function, is a fluorophore that emits a fluorescence signal when excited with near infrared light (750-810 nm) (2). The dye binds to plasma albumin and has been used intra-operatively to evaluate graft perfusion, aneurysm clipping, and lymphatic mapping. ICG undergoes hepatic metabolism and is excreted by hepatocytes into the biliary tract after approximately 6 h. Due to the impaired biliary excretion of hepatic malignancies compared to normal hepatocytes, ICG is preferentially retained in or around these lesions over time, allowing surgeons to visualize the fluorescent signal and identify the tumor over the liver (3).For patients undergoing pre-operative ICG hepatic function testing several days before surgery, surface hepatic lesions can be visualized with a positive fluorescence signal. There is sufficient contrast as the ICG is retained at the lesions and ICG in the surrounding normal hepatocytes will have been excreted out in the biliary tract. The dye is versatile in that it can additionally be used as an angiographic agent when injected into portal vasculature, similar to indigo-carmine or methylene blue (4). Rather than the quick washout of the traditional dyes, the NIR signal from ICG persists throughout the surgical procedure, allowing for continued image guidance. Positive segmental staining can be obtained by selective portal vein injection while negative segmental staining can be obtained by intravenous injection during selective portal clamping. Realtime intra-operative selective segmental staining, along with contrasted-target identification, allows surgeons to more effectively resect hepatic neoplasms.In the article titled "Applications of fusion-fluorescence imaging using indocyanine green in laparoscopic hepatectomy," Terasawa et al. describe the use of ICG-fl...

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Tumor-Specific Fluorescence Antibody Imaging Enables Accurate Staging Laparoscopy in an Orthotopic Model of Pancreatic Cancer

Cited by 41 publications

References 22 publications

Fluorescence-guided Surgery with a Fluorophore-conjugated Antibody to Carcinoembryonic Antigen (CEA), that Highlights the Tumor, Improves Surgical Resection and Increases Survival in Orthotopic Mouse Models of Human Pancreatic Cancer

Fluorescence-guided Surgery with a Fluorophore-conjugated Antibody to Carcinoembryonic Antigen (CEA), that Highlights the Tumor, Improves Surgical Resection and Increases Survival in Orthotopic Mouse Models of Human Pancreatic Cancer

SPECT- and Fluorescence Image–Guided Surgery Using a Dual-Labeled Carcinoembryonic Antigen–Targeting Antibody

Regarding the applications of fusion-fluorescence imaging using indocyanine green in laparoscopic hepatectomy

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