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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sawada, Ritsuko Houghton, Jacob L. Zeglis, Brian M. Agnew, Brian J. Aggeler, Robert Scholz, Wolfgang W. Abdel-atti, Dalya Lewis, Jason S. |
| Description | Author Affiliation: Houghton JL ( Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10075); Zeglis BM ( Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10075); Abdel-Atti D ( Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10075); Aggeler R ( Foundational Biology Group, Thermo Fisher Scientific, Eugene, OR 97402); Sawada R ( Mabvax, San Diego, CA 92121.); Agnew BJ ( Foundational Biology Group, Thermo Fisher Scientific, Eugene, OR 97402); Scholz WW ( Mabvax, San Diego, CA 92121.); Lewis JS ( Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY 10075); |
| Abstract | Molecular imaging agents for preoperative positron emission tomography (PET) and near-infrared fluorescent (NIRF)-guided delineation of surgical margins could greatly enhance the diagnosis, staging, and resection of pancreatic cancer. PET and NIRF optical imaging offer complementary clinical applications, enabling the noninvasive whole-body imaging to localize disease and identification of tumor margins during surgery, respectively. We report the development of PET, NIRF, and dual-modal (PET/NIRF) imaging agents, using 5B1, a fully human monoclonal antibody that targets CA19.9, a well-established pancreatic cancer biomarker. Desferrioxamine (DFO) and/or a NIRF dye (FL) were conjugated to the heavy-chain glycans of 5B1, using a robust and reproducible site-specific (ss) labeling methodology to generate three constructs ((ss)DFO-5B1, (ss)FL-5B1, and (ss)dual-5B1) in which the immunoreactivity was not affected by the conjugation of either label. Each construct was evaluated in a s.c. xenograft model, using CA19.9-positive (BxPC3) and -negative (MIAPaCa-2) human pancreatic cancer cell lines. Each construct showed exceptional uptake and contrast in antigen-positive tumors with negligible nonspecific uptake in antigen-negative tumors. Additionally, the dual-modal construct was evaluated in an orthotopic murine pancreatic cancer model, using the human pancreatic cancer cell line, Suit-2. The (ss)dual-5B1 demonstrated a remarkable capacity to delineate metastases and to map the sentinel lymph nodes via tandem PET-computed tomography (PET/CT) and NIRF imaging. Fluorescence microscopy, histopathology, and autoradiography were performed on representative sections of excised tumors to visualize the distribution of the constructs within the tumors. These imaging tools have tremendous potential for further preclinical research and for clinical translation. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 52 |
| Volume Number | 112 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2015-12-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CA-19-9 Antigen Immunology Immunoconjugates Multimodal Imaging Pancreatic Neoplasms Metabolism Positron-Emission Tomography Spectroscopy, Near-Infrared Animals Antibodies, Monoclonal Pharmacokinetics Cell Line, Tumor Deferoxamine Chemistry Disease Models, Animal Fluorescent Dyes Mice, Knockout Mice, Nude Microscopy, Fluorescence Molecular Structure Diagnosis Radioisotopes Reproducibility Of Results Sensitivity And Specificity Tissue Distribution Transplantation, Heterologous Zirconium Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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