Imaging of Primary and Metastatic Pancreatic Cancer Using a Fluorophore‐Conjugated Anti‐CA19‐9 Antibody for Surgical Navigation

McElroy, Michele; Kaushal, Sharmeela; Luiken, George A.; Talamini, Mark A.; Moossa, A. R.; Hoffman, Robert M.; Bouvet, Michael

doi:10.1007/s00268-007-9452-1

Cited by 94 publications

(88 citation statements)

References 36 publications

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“…From a molecular-imaging perspective, ACPPDs have several advantages over other targeted fluorescent probes previously described in the literature for use in a surgical system (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Molecular fluorescence-guided surgery demands that a given probe (a), works for a wide variety of tumor types (b), offers ample signal with low background (c), binds tightly to the tumor, and (d), is not affected by the physical trauma of surgery.…”

Section: Discussionmentioning

confidence: 99%

“…Molecular fluorescence-guided surgery demands that a given probe (a), works for a wide variety of tumor types (b), offers ample signal with low background (c), binds tightly to the tumor, and (d), is not affected by the physical trauma of surgery. Although antibody approaches to fluorescence-guided surgery are attractive for individual tumor types that express unique surface markers such as colon (15), pancreas (16), or ovary (17), they are often not applicable to all tumor types. Most tumor antigens such as CEA and CA19-9 have no known etiological function, as demonstrated by their frequent elimination during passage in culture.…”

Section: Discussionmentioning

confidence: 99%

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Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival

Nguyen

Olson

Aguilera

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

441

310

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The completeness of tumor removal during surgery is dependent on the surgeon's ability to differentiate tumor from normal tissue using subjective criteria that are not easily quantifiable. A way to objectively assess tumor margins during surgery in patients would be of great value. We have developed a method to visualize tumors during surgery using activatable cell-penetrating peptides (ACPPs), in which the fluorescently labeled, polycationic cell-penetrating peptide (CPP) is coupled via a cleavable linker to a neutralizing peptide. Upon exposure to proteases characteristic of tumor tissue, the linker is cleaved, dissociating the inhibitory peptide and allowing the CPP to bind to and enter tumor cells. In mice, xenografts stably transfected with green fluorescent protein show colocalization with the Cy5-labeled ACPPs. In the same mouse models, Cy5-labeled free ACPPs and ACPPs conjugated to dendrimers (ACPPDs) delineate the margin between tumor and adjacent tissue, resulting in improved precision of tumor resection. Surgery guided by ACPPD resulted in fewer residual cancer cells left in the animal after surgery as measured by Alu PCR. A single injection of ACPPD dually labeled with Cy5 and gadolinium chelates enabled preoperative wholebody tumor detection by MRI, intraoperative guidance by real-time fluorescence, intraoperative histological analysis of margin status by fluorescence, and postoperative MRI tumor quantification. Animals whose tumors were resected with ACPPD guidance had better long-term tumor-free survival and overall survival than animals whose tumors were resected with traditional bright-field illumination only.intraoperative fluorescence imaging | molecular navigation | long-term survival | molecular imaging | surgical margin

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival

Nguyen

Olson

Aguilera

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

441

310

View full text Add to dashboard Cite

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“…[8][9][10][12][13][14][15] In this study, we determined the fluorophores that would optimize tumor labeling. The high-fluorescence intensity, lack of anomalous peaks, and high quantum yields of Alexa Fluor and DyLight dyes, compared to dyes with comparable spectra are important features.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6][7][8][9][10][11] In an effort to bring FGS to the clinic, we have performed FGS in orthotopic mouse models of pancreatic and colon cancers, labeled with tumor-specific monoclonal mouse antibodies conjugated to Alexa Fluor 488, a green fluorophore. 12,13 In subsequent studies, minimally invasive fluorescence laparoscopy was used to image orthotopic pancreatic tumors in mice labeled with fluorophore-conjugated monoclonal mouse antibodies to CEA. 14,15 However, there remains uncertainty regarding the choice of the appropriate fluorophore for optimal imaging of pancreatic cancer with fluorophore-conjugated antibodies.…”

Section: Introductionmentioning

confidence: 99%

Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with visible or near-infrared fluorescent dyes for imaging pancreatic cancer in orthotopic nude mouse models

et al. 2013

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Abstract. The aim of this study was to evaluate a set of visible and near-infrared dyes conjugated to a tumor-specific chimeric antibody for high-resolution tumor imaging in orthotopic models of pancreatic cancer. BxPC-3 human pancreatic cancer was orthotopically implanted into pancreata of nude mice. Mice received a single intravenous injection of a chimeric anti-carcinoembryonic antigen antibody conjugated to one of the following fluorophores: 488-nm group (Alexa Fluor 488 or DyLight 488); 550-nm group (Alexa Fluor 555 or DyLight 550); 650-nm group (Alexa Fluor 660 or DyLight 650), or the 750-nm group (Alexa Fluor 750 or DyLight 755). After 24 h, the Olympus OV100 small-animal imaging system was used for noninvasive and intravital fluorescence imaging of mice. Dyes were compared with respect to depth of imaging, resolution, tumor-to-background ratio (TBR), photobleaching, and hemoglobin quenching. The longer wavelength dyes had increased depth of penetration and ability to detect the smallest tumor deposits and provided the highest TBRs, resistance to hemoglobin quenching, and specificity. The shorter wavelength dyes were more photostable. This study showed unique advantages of each dye for specific cancer imaging in a clinically relevant orthotopic model.

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“…Our laboratory has pioneered mouse models using fluorescent proteins, as well as fluorescent antibodies, to label tumors for FGS (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11).…”

mentioning

confidence: 99%

Color-coded Imaging Enables Fluorescence-guided Surgery to Resect the Tumor Along with the Tumor Microenvironment in a Syngeneic Mouse Model of EL-4 Lymphoma

Hasegawa

Suetsugu

Nakamura

et al. 2016

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Abstract. Background Fluorescence-guided surgery (FGS) of cancer is an emerging technology. Our laboratory has pioneered mouse models using fluorescent proteins, as well as fluorescent antibodies, to label tumors for FGS (1-11).To achieve complete tumor resection, it is necessary to understand the relationship between cancer cells and stromal cells in the tumor microenvironment (TME) (9). We previously reported imaging of the TME during tumor progression and metastasis by color-coding cancer and stromal cells (12-27).We have subsequently used genetic reporters to color code cancer and stroma cells in a patient-derived orthotopic xenograft (PDOX) model. Cancer cells were labeled with a telomerasedependent green fluorescent protein (GFP)-containing adenovirus (OBP-401) in a pancreatic cancer PDOX. The PDOX was labeled in the stroma by red fluorescent protein (RFP) during growth in transgenic mice that express RFP (9).In the present report, we developed a color-coded syngeneic model for FGS using a mouse lymphoma cell line (EL-4), expressing RFP, and transgenic C57/B6 mice ubiquitously expressing GFP under the control of the chicken β-actin promoter and cytomegalovirus enhancer. Using the portable, hand-held Dino-Lite fluorescence microscope, the EL-4-RFP tumor in the GFP mouse was color-coded imaged in order to visualize the tumor and TME and resected by FGS. Confocal microscopy of the resected tumor demonstrated that both tumor and the TME were completely resected by color-coded FGS. In the resected RFP-expressing tumor, various types of GFPexpressing stromal cells were observed intermingling with the cancer cells in the TME. 4443

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Imaging of Primary and Metastatic Pancreatic Cancer Using a Fluorophore‐Conjugated Anti‐CA19‐9 Antibody for Surgical Navigation

Cited by 94 publications

References 36 publications

Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival

Surgery with molecular fluorescence imaging using activatable cell-penetrating peptides decreases residual cancer and improves survival

Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with visible or near-infrared fluorescent dyes for imaging pancreatic cancer in orthotopic nude mouse models

Color-coded Imaging Enables Fluorescence-guided Surgery to Resect the Tumor Along with the Tumor Microenvironment in a Syngeneic Mouse Model of EL-4 Lymphoma

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