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      CA19-9 as a Potential Target for Radiolabeled Antibody-Based Positron Emission Tomography of Pancreas Cancer

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          Abstract

          Introduction. Sensitive and specific imaging of pancreas cancer are necessary for accurate diagnosis, staging, and treatment. The vast majority of pancreas cancers express the carbohydrate tumor antigen CA19-9. The goal of this study was to determine the potential to target CA19-9 with a radiolabeled anti-CA19-9 antibody for imaging pancreas cancer. Methods. CA19-9 was quantified using flow cytometry on human pancreas cancer cell lines. An intact murine anti-CA19-9 monoclonal antibody was labeled with a positron emitting radionuclide (Iodine-124) and injected into mice harboring antigen positive and negative xenografts. MicroPET/CT were performed at successive time intervals (72 hours, 96 hours, 120 hours) after injection. Radioactivity was measured in blood and tumor to provide objective confirmation of the images. Results. Antigen expression by flow cytometry revealed approximately 1.3 × 10 6 CA19-9 antigens for the positive cell line and no expression in the negative cell line. Pancreas xenograft imaging with Iodine-124-labeled anti-CA19-9 mAb demonstrated an average tumor to blood ratio of 5 and positive to negative tumor ratio of 20. Conclusion. We show in vivo targeting of our antigen positive xenograft with a radiolabeled anti-CA19-9 antibody. These data demonstrate the potential to achieve anti-CA19-9 antibody based positron emission tomography of pancreas cancer.

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          Most cited references31

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          Nanoparticle and targeted systems for cancer therapy.

          This review explores recent work directed towards more targeted treatment of cancer, whether through more specific anti-cancer agents or through methods of delivery. These areas include delivery by avoiding the reticuloendothelial system, utilizing the enhanced permeability and retention effect and tumor-specific targeting. Treatment opportunities using antibody-targeted therapies are summarized. The ability to treat cancer by targeting delivery through angiogenesis is also discussed and antiangiogenic drugs in clinical trials are presented. Delivery methods that specifically use nanoparticles are also highlighted, including both degradable and nondegradable polymers.
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            AMIDE: a free software tool for multimodality medical image analysis.

            Amide's a Medical Image Data Examiner (AMIDE) has been developed as a user-friendly, open-source software tool for displaying and analyzing multimodality volumetric medical images. Central to the package's abilities to simultaneously display multiple data sets (e.g., PET, CT, MRI) and regions of interest is the on-demand data reslicing implemented within the program. Data sets can be freely shifted, rotated, viewed, and analyzed with the program automatically handling interpolation as needed from the original data. Validation has been performed by comparing the output of AMIDE with that of several existing software packages. AMIDE runs on UNIX, Macintosh OS X, and Microsoft Windows platforms, and it is freely available with source code under the terms of the GNU General Public License.
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              Molecular imaging: current status and emerging strategies.

              In vivo molecular imaging has a great potential to impact medicine by detecting diseases in early stages (screening), identifying extent of disease, selecting disease- and patient-specific treatment (personalized medicine), applying a directed or targeted therapy, and measuring molecular-specific effects of treatment. Current clinical molecular imaging approaches primarily use positron-emission tomography (PET) or single photon-emission computed tomography (SPECT)-based techniques. In ongoing preclinical research, novel molecular targets of different diseases are identified and, sophisticated and multifunctional contrast agents for imaging these molecular targets are developed along with new technologies and instrumentation for multi-modality molecular imaging. Contrast-enhanced molecular ultrasound (US) with molecularly-targeted contrast microbubbles is explored as a clinically translatable molecular imaging strategy for screening, diagnosing, and monitoring diseases at the molecular level. Optical imaging with fluorescent molecular probes and US imaging with molecularly-targeted microbubbles are attractive strategies as they provide real-time imaging, are relatively inexpensive, produce images with high spatial resolution, and do not involve exposure to ionizing irradiation. Raman spectroscopy/microscopy has emerged as a molecular optical imaging strategy for ultrasensitive detection of multiple biomolecules/biochemicals with both in vivo and ex vivo versatility. Photoacoustic imaging is a hybrid of optical and US techniques involving optically-excitable molecularly-targeted contrast agents and quantitative detection of resulting oscillatory contrast agent movement with US. Current preclinical findings and advances in instrumentation, such as endoscopes and microcatheters, suggest that these molecular imaging methods have numerous potential clinical applications and will be translated into clinical use in the near future. Copyright 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Int J Mol Imaging
                IJMI
                International Journal of Molecular Imaging
                Hindawi Publishing Corporation
                2090-1712
                2090-1720
                2011
                6 September 2011
                : 2011
                : 834515
                Affiliations
                1Department of Surgery, UCLA, 10833 LeConte Avenue, Rm 54-140, Los Angeles, CA 90095, USA
                2Department of Surgery, Veterans Affairs Greater Los Angeles, Health Care Center, Los Angeles, CA 90073, USA
                3Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, Los Angeles, CA 90095, USA
                Author notes

                Academic Editor: Ronald L. Van Heertum

                Article
                10.1155/2011/834515
                3168788
                21912743
                f3b45a75-7ac8-41f7-9966-cb3f296dd2a8
                Copyright © 2011 Mark D. Girgis et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 5 May 2011
                : 3 July 2011
                Categories
                Research Article

                Molecular biology
                Molecular biology

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