Fluorescence‐ and multispectral optoacoustic imaging for an optimized detection of deeply located tumors in an orthotopic mouse model of pancreatic carcinoma |
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| Authors: | Jing Claussen Hendrica AJM Prevoo Cornelis FM Sier Freek JM Hoeben Marc S Robillard Alexander L Vahrmeijer Tim Devling Alan B Chan Lioe‐Fee de Geus‐Oei Frauke Alves |
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| Institution: | 1. iThera Medical GmbH, Zielstattstrasse, Munich, Germany;2. Antibodies for Research Applications B.V., HT Gouda, The Netherlands;3. SyMO‐Chem, Het Kranenveld 14, AZ Eindhoven, The Netherlands;4. Tagworks Pharmaceuticals, Geert Grooteplein Zuid 10, GA Nijmegen, The Netherlands;5. Department of Surgery, Leiden University Medical Center, RC Leiden, The Netherlands;6. Percuros B.V., AE Enschede, The Netherlands;7. Department of Radiology, Leiden University Medical Center, RC Leiden, The Netherlands;8. Biomedical Photonic Imaging Group, MIRA Institute, University of Twente, AE Enschede, The Netherlands;9. Institute of Interventional and Diagnostic Radiology, University Medical Center G?ttingen, G?ttingen, Lower Saxony, Germany;10. Clinic of Haematology and Medical Oncology, University Medical Center G?ttingen, G?ttingen, Lower Saxony, Germany;11. Translational Molecular Imaging, Max‐Planck‐Institute of Experimental Medicine, G?ttingen, Lower Saxony, Germany |
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| Abstract: | A crucial point for the management of pancreatic ductal adenocarcinoma (PDAC) is the decrease of R1 resections. Our aim was to evaluate the combination of multispectral optoacoustic tomography (MSOT) with fluorescence guided surgery (FGS) for diagnosis and perioperative detection of tumor nodules and resection margins in a xenotransplant mouse model of human pancreatic cancer. The peptide cRGD, conjugated with the near infrared fluorescent (NIRF) dye IRDye800CW and with a trans‐cyclooctene (TCO) tag for future click chemistry (cRGD‐800CW‐TCO), was applied to PDAC bearing immunodeficient nude mice; 27 days after orthotopic transplantation of human AsPC‐1 cells into the head of the pancreas, mice were injected with cRGD‐800CW‐TCO and imaged with fluorescence‐ and optoacoustic devices before and 2, 6 and 24 hr after injection, before they were sacrificed and dissected with a guidance of FGS imaging system. Fluorescence imaging of cRGD‐800CW‐TCO allowed detection of the tumor area but without information about the depth, whereas MSOT allowed high resolution 3 D identification of the tumor area, in particular of small tumor nodules. Highly sensitive delineation of tumor burden was achieved during FGS in all mice. Imaging of whole‐mouse cryosections, histopathological analysis and NIRF microscopy confirmed the localization of cRGD‐800CW‐TCO within the tumor tissue. In principle, all imaging modalities applied here were able to detect PDAC in vivo. However, the combination of MSOT and FGS provided detailed spatial information of the signal and achieved a complete overview of the distribution and localization of cRGD‐800CW‐TCO within the tumor before and during surgical intervention. |
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| Keywords: | optoacoustic imaging fluorescence guided surgery optical imaging pancreatic ductal adenocarcinoma cyclic arginine– glycine– aspartic acid (cRGD) |
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