Lingyi Sun1,2, Yongkang Gai3, Zhonghan Li4, Huiqiang Li3, Jianchun Li3, John Muschler5, Rui Kang6, Daolin Tang6, Dexing Zeng7,8. 1. Department of Diagnostic Radiology, Oregon Health & Science University, Portland, OR, 97229, USA. sunl@ohsu.edu. 2. Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA. sunl@ohsu.edu. 3. Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA. 4. Department of Diagnostic Radiology, Oregon Health & Science University, Portland, OR, 97229, USA. 5. Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, 97229, USA. 6. Department of Surgery, UT Southwestern Medical Center, Dallas, TX, 75390, USA. 7. Department of Diagnostic Radiology, Oregon Health & Science University, Portland, OR, 97229, USA. dexingzeng@outlook.com. 8. Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA. dexingzeng@outlook.com.
Abstract
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal gastrointestinal cancer, and its poor prognosis is highly associated with the lack of an efficient early detection technology. Here, we report that RGD-NGR heterodimer labeled with PET isotope could be applied in PDAC early detection. PROCEDURES: The RGD-NGR tracer was first compared with its corresponding monomeric counterparts via PET imaging studies using mice bearing a subcutaneous BxPC3 tumor. Subsequently, the RGD-NGR tracer was evaluated in autochthonous mouse models with spontaneously developed late stage PanIN lesions (KCER mice) or PDAC (KPC mice) via both PET imaging studies and ex vivo biodistribution studies. Furthermore, a comparison between 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) and the RGD-NGR tracer was conducted via PET imaging of the same KCH mouse bearing spontaneously developed PDAC. H&E staining was performed to confirm the malignant pancreatic tissue in the KCH mouse. Immunofluorescence staining was performed to confirm the expression of integrin αVβ3 and CD13. RESULTS: The RGD-NGR tracer exhibited improved in vivo performance as compared with its corresponding monomeric counterparts on the subcutaneous BxPC3 tumor mouse model. Subsequent evaluation in autochthonous mouse models demonstrated its capability to detect both pre-malignant and malignant pancreases. Further comparison with [18F]F-FDG revealed the superiority of the proposed heterodimer in imaging spontaneously developed PDAC. H&E staining confirmed the malignant pancreatic tissue in the KCH mouse, while the expression of both integrin αVβ3 and CD13 receptors was demonstrated with immunofluorescence staining. CONCLUSION: The proposed RGD-NGR heterodimer possesses the potential to be applied in the PDAC early detection for high-risk populations.
PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal gastrointestinal cancer, and its poor prognosis is highly associated with the lack of an efficient early detection technology. Here, we report that RGD-NGR heterodimer labeled with PET isotope could be applied in PDAC early detection. PROCEDURES: The RGD-NGR tracer was first compared with its corresponding monomeric counterparts via PET imaging studies using mice bearing a subcutaneous BxPC3 tumor. Subsequently, the RGD-NGR tracer was evaluated in autochthonous mouse models with spontaneously developed late stage PanIN lesions (KCER mice) or PDAC (KPC mice) via both PET imaging studies and ex vivo biodistribution studies. Furthermore, a comparison between 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) and the RGD-NGR tracer was conducted via PET imaging of the same KCH mouse bearing spontaneously developed PDAC. H&E staining was performed to confirm the malignant pancreatic tissue in the KCH mouse. Immunofluorescence staining was performed to confirm the expression of integrin αVβ3 and CD13. RESULTS: The RGD-NGR tracer exhibited improved in vivo performance as compared with its corresponding monomeric counterparts on the subcutaneous BxPC3 tumor mouse model. Subsequent evaluation in autochthonous mouse models demonstrated its capability to detect both pre-malignant and malignant pancreases. Further comparison with [18F]F-FDG revealed the superiority of the proposed heterodimer in imaging spontaneously developed PDAC. H&E staining confirmed the malignant pancreatic tissue in the KCH mouse, while the expression of both integrin αVβ3 and CD13 receptors was demonstrated with immunofluorescence staining. CONCLUSION: The proposed RGD-NGR heterodimer possesses the potential to be applied in the PDAC early detection for high-risk populations.
Authors: Everardo D Saad; Marcel C Machado; Dalia Wajsbrot; Roberto Abramoff; Paulo M Hoff; Jacques Tabacof; Artur Katz; Sergio D Simon; René C Gansl Journal: Int J Gastrointest Cancer Date: 2002
Authors: Sunil R Hingorani; Emanuel F Petricoin; Anirban Maitra; Vinodh Rajapakse; Catrina King; Michael A Jacobetz; Sally Ross; Thomas P Conrads; Timothy D Veenstra; Ben A Hitt; Yoshiya Kawaguchi; Don Johann; Lance A Liotta; Howard C Crawford; Mary E Putt; Tyler Jacks; Christopher V E Wright; Ralph H Hruban; Andrew M Lowy; David A Tuveson Journal: Cancer Cell Date: 2003-12 Impact factor: 31.743
Authors: John P Neoptolemos; Deborah D Stocken; Helmut Friess; Claudio Bassi; Janet A Dunn; Helen Hickey; Hans Beger; Laureano Fernandez-Cruz; Christos Dervenis; François Lacaine; Massimo Falconi; Paolo Pederzoli; Akos Pap; David Spooner; David J Kerr; Markus W Büchler Journal: N Engl J Med Date: 2004-03-18 Impact factor: 91.245