San Diego, CA, United States
San Diego, CA, United States

Time filter

Source Type

Metildi C.A.,University of California at San Diego | Kaushal S.,University of California at San Diego | Lee C.,UVP | Hardamon C.R.,University of California at San Diego | And 6 more authors.
Journal of the American College of Surgeons | Year: 2012

Background: The aim of this study was to improve fluorescence laparoscopy of pancreatic cancer in an orthotopic mouse model with the use of a light-emitting diode (LED) light source and optimal fluorophore combinations. Study Design: Human pancreatic cancer models were established with fluorescent FG-RFP, MiaPaca2-GFP, BxPC-3-RFP, and BxPC-3 cancer cells implanted in 6-week-old female athymic mice. Two weeks postimplantation, diagnostic laparoscopy was performed with a Stryker L9000 LED light source or a Stryker X8000 xenon light source 24 hours after tail-vein injection of CEA antibodies conjugated with Alexa 488 or Alexa 555. Cancer lesions were detected and localized under each light mode. Intravital images were also obtained with the OV-100 Olympus and Maestro CRI Small Animal Imaging Systems, serving as a positive control. Tumors were collected for histologic analysis. Results: Fluorescence laparoscopy with a 495-nm emission filter and an LED light source enabled real-time visualization of the fluorescence-labeled tumor deposits in the peritoneal cavity. The simultaneous use of different fluorophores (Alexa 488 and Alexa 555), conjugated to antibodies, brightened the fluorescence signal, enhancing detection of submillimeter lesions without compromising background illumination. Adjustments to the LED light source permitted simultaneous detection of tumor lesions of different fluorescent colors and surrounding structures with minimal autofluorescence. Conclusions: Using an LED light source with adjustments to the red, blue, and green wavelengths, it is possible to simultaneously identify tumor metastases expressing fluorescent proteins of different wavelengths, which greatly enhanced the signal without compromising background illumination. Development of this fluorescence laparoscopy technology for clinical use can improve staging and resection of pancreatic cancer. © 2012 American College of Surgeons.


Metildi C.A.,University of California at San Diego | Kaushal S.,University of California at San Diego | Pu M.,University of California at San Diego | Messer K.A.,University of California at San Diego | And 6 more authors.
Annals of Surgical Oncology | Year: 2014

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. © 2014 Society of Surgical Oncology.


Metildi C.A.,University of California at San Diego | Kaushal S.,University of California at San Diego | Luiken G.A.,OncoFluor Inc. | Hoffman R.M.,University of California at San Diego | And 2 more authors.
Journal of the American College of Surgeons | Year: 2014

Background Our laboratory has previously developed fluorescence-guided surgery of pancreatic and other cancers in orthotopic mouse models. Laparoscopic surgery is being used more extensively in surgical oncology. This report describes the efficacy of laparoscopic fluorescence-guided surgery of pancreatic cancer in an orthotopic mouse model. Study Design Mouse models of human pancreatic cancer were established with fragments of the BxPC-3 red fluorescent protein-expressing human pancreatic cancer using surgical orthotopic implantation. Mice were randomized to bright-light laparoscopic surgery (BLLS) or to fluorescence-guided laparoscopic surgery (FGLS). Fluorescence-guided laparoscopic surgery was performed with a light-emitting diode light source through a 495-nm emission filter in order to resect the primary tumors and any additional separate submillimeter tumor deposits within the pancreas, the latter of which was not possible with BLLS. Tumors were labeled with anti-CEA AlexaFluor 488 antibodies 24 hours before surgery with intravenous injection. Perioperative fluorescence images were obtained to evaluate tumor size. Mice were followed postoperatively to assess for recurrence and at termination to evaluate tumor burden. Results At termination, the FGLS-treated mice had less pancreatic tumor volume than the BLLS-treated mice (5.75 mm2 vs 28.43 mm2, respectively; p = 0.012) and lower tumor weight (21.1 mg vs 174.4 mg, respectively; p = 0.033). Fluorescence-guided laparoscopic surgery compared with BLLS also decreased local recurrence (50% vs 80%, respectively; p = 0.048) and distant recurrence (70% vs 95%, respectively; p = 0.046). More mice in the FGLS group than the BLLS group were free of tumor at termination (25% vs 5%, respectively). Median disease-free survival was lengthened from 2 weeks with BLLS (95% CI, 1.635-2.365) to 7 weeks with FGLS (95% CI, 5.955-8.045; p = 0.001). Conclusions Fluorescence-guided laparoscopic surgery is more effective than BLLS and, therefore, has important potential for surgical oncology. © 2014 by the American College of Surgeons.


Metildi C.A.,University of California at San Diego | Kaushal S.,University of California at San Diego | Luiken G.A.,OncoFluor Inc | Talamini M.A.,University of California at San Diego | And 4 more authors.
Journal of Surgical Oncology | Year: 2014

Background and Objectives The aim of this study was to evaluate a new fluorescently labeled chimeric anti-CEA antibody for improved detection and resection of colon cancer. Methods Frozen tumor and normal human tissue samples were stained with chimeric and mouse antibody-fluorophore conjugates for comparison. Mice with patient-derived orthotopic xenografts (PDOX) of colon cancer underwent fluorescence-guided surgery (FGS) or bright-light surgery (BLS) 24 hr after tail vein injection of fluorophore-conjugated chimeric anti-CEA antibody. Resection completeness was assessed using postoperative images. Mice were followed for 6 months for recurrence. Results The fluorophore conjugation efficiency (dye/mole ratio) improved from 3-4 to >5.5 with the chimeric CEA antibody compared to mouse anti-CEA antibody. CEA-expressing tumors labeled with chimeric CEA antibody provided a brighter fluorescence signal on frozen human tumor tissues (P = 0.046) and demonstrated consistently lower fluorescence signals in normal human tissues compared to mouse antibody. Chimeric CEA antibody accurately labeled PDOX colon cancer in nude mice, enabling improved detection of tumor margins for more effective FGS. The R0 resection rate increased from 86% to 96% with FGS compared to BLS. Conclusion Improved conjugating efficiency and labeling with chimeric fluorophore-conjugated antibody resulted in better detection and resection of human colon cancer in an orthotopic mouse model. © 2013 Wiley Periodicals, Inc.


Maawy A.A.,University of California at San Diego | Hiroshima Y.,Yokohama City University | Zhang Y.,Anticancer, Inc. | Luiken G.A.,OncoFluor Inc. | And 2 more authors.
Journal of biomedical optics | Year: 2014

Labeling of metastatic tumors can aid in their staging and resection of cancer. Near infrared (NIR) dyes have been used in the clinic for tumor labeling. However, there can be a nonspecific uptake of dye by the liver, lungs, and lymph nodes, which hinders detection of metastasis. In order to overcome these problems, we have used two NIR dyes (DyLight 650 and 750) conjugated to a chimeric anti-carcinoembryonic antigen antibody to evaluate how polyethylene glycol linkage (PEGylation) can improve specific tumor labeling in a nude mouse model of human pancreatic cancer. The conjugated PEGylated and non-PEGylated DyLight 650 and 750 dyes were injected intravenously into non-tumor-bearing nude mice. Serum samples were collected at various time points in order to determine serum concentrations and elimination kinetics. Conjugated PEGylated dyes had significantly higher serum dye concentrations than non-PEGylated dyes (p=0.005 for the 650 dyes and p<0.001 for the 750 dyes). Human pancreatic tumors subcutaneously implanted into nude mice were labeled with antibody-dye conjugates and serially imaged. Labeling with conjugated PEGylated dyes resulted in significantly brighter tumors compared to the non-PEGylated dyes (p<0.001 for the 650 dyes; p=0.01 for 750 dyes). PEGylation of the NIR dyes also decreased their accumulation in lymph nodes, liver, and lung. These results demonstrate enhanced selective tumor labeling by PEGylation of dyes conjugated to a tumor-specific antibody, suggesting their future clinical use in fluorescence-guided surgery.


Trademark
OncoFluor Inc. | Date: 2010-02-09

pharmaceutical preparation, namely, monoclonal antibody for the treatment of cancer.


Trademark
OncoFluor Inc. | Date: 2010-02-09

pharmaceutical preparation, namely, monoclonal antibody for the treatment of cancer.


Endoscopic devices and methods for imaging and treating organs and tissues are described. The endoscopic devices described herein include flexible endoscopes, rigid endoscopes, and capsule endoscopes. The endoscopic device may comprise one or more cameras and one or more light sources. In some embodiments, the endoscopic device comprises at least one white light camera, at least one blue light camera, at least one white light source, and at least one blue light source. In some embodiments, fluorescent targeting constructs can be injected into the subject and bound to and/or taken up by a tumor or diseased tissue. Diseased tissue can be identified by viewing the fluorescence emanating from the fluorescent targeting constructs by illuminating an in vivo body part of the subject with light having at least one excitation wavelength in the range from 400 nm to about 510 nm.


Patent
Oncofluor Inc. | Date: 2014-08-25

The present invention provides methods and compositions for detecting and treating malignant tissue, organs or cells in a mammal. The method comprises parenterally injecting a mammalian subject, at a locus or by a route providing access to the tissue or organ, with a composition comprising a monoclonal antibody (chimeric, humanized, fully human), partial antibody, Fab Fragment, antibody fragment that is tagged with a fluorophore with or without the addition of a therapeutic chemotherapy molecule, which specifically binds to the targeted organ, tissue or cell. Resection of the primary malignant tissue within the mammalian species (using the fluorescence of the fluorescing targeting construct) provides the advantage of identifying all bulk tumor as fluorescent at the time of the original tumor resection. Additional (adjuvant) therapy is provided by the chemotherapy molecule that is bound to the fluorescent-tagged monoclonal antibody (or antibody part thereof that is bound to small, microscopic clusters of cells (circulating tumor cells or tissue bound small microscopic clusters of cells) that are not visible to the naked eye and that could not be seen with the aid of the excitation light source and a magnification device. Chemotherapy molecules bound to the fluorescent-tagged monoclonal antibody construct provide the additional benefit of killing off the malignant cells that might be undetected using just the excitation light source for surgical resection.


Patent
Oncofluor Inc. | Date: 2012-01-25

The present invention provides methods and compositions for detecting and treating malignant tissue, organs or cells in a mammal. The method comprises parenterally injecting a mammalian subject, at a locus or by a route providing access to the tissue or organ, with a composition comprising a monoclonal antibody (chimeric, humanized, fully human), partial antibody, Fab Fragment, antibody fragment that is tagged with a fluorophore with or without the addition of a therapeutic chemotherapy molecule, which specifically binds to the targeted organ, tissue or cell. Resection of the primary malignant tissue within the mammalian species (using the fluorescence of the fluorescing targeting construct) provides the advantage of identifying all bulk tumor as fluorescent at the time of the original tumor resection.

Loading OncoFluor Inc. collaborators
Loading OncoFluor Inc. collaborators