Fluorescence‐ and multispectral optoacoustic imaging for an optimized detection of deeply located tumors in an orthotopic mouse model of pancreatic carcinoma. Issue 10 (19th January 2018)

• Record Type: Journal Article
• Authors: Napp, Joanna; Stammes, Marieke A.; Claussen, Jing; Prevoo, Hendrica A.J.M.; Sier, Cornelis F.M.; Hoeben, Freek J.M.; Robillard, Marc S.; Vahrmeijer, Alexander L.; Devling, Tim; Chan, Alan B.; de Geus‐Oei, Lioe‐Fee; Alves, Frauke
• Is Part Of: International journal of cancer. Volume 142:Issue 10(2018)
• Page Start: 2118
• Page End: 2129
• Publication Date: 2018-01-19
• Subjects: optoacoustic imaging -- fluorescence guided surgery -- optical imaging -- pancreatic ductal adenocarcinoma -- cyclic arginine–glycine–aspartic acid (cRGD); Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.31236
• Languages: English
• ISSNs: 0020-7136

Abstract

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. Abstract : What's new? Pancreatic cancer has poor prognosis, because it initially causes few symptoms, and it's very aggressive. When tumors are surgically removed, microscopic remnants frequently remain, enabling the cancer to return. Advanced imaging techniques, such as fluorescence guided surgery, help surgeons see the boundary between healthy and tumor tissue. Here, the authors demonstrate the effectiveness of multispectral imaging tomography (MSOT) in combination with an integrin‐targeting fluorescent probe to collect high resolution 3 D images of pancreatic tumors to be excised. This is the first study showing the unique ability of MSOT to provide detailed information about widespread pancreatic tumors prior to surgery.