Gastroenterology
Volume 136, Issue 5 , Pages 1514-1525.e2 , May 2009

Molecular Imaging of Pancreatic Cancer in an Animal Model Using Targeted Multifunctional Nanoparticles

  • Lily Yang

      Affiliations

    • Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
    • Department of Radiology, Emory University School of Medicine, Atlanta, Georgia
    • Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
    • Corresponding Author InformationReprint requests Address requests for reprints to: Lily Yang, MD, PhD, Department of Surgery and Winship Cancer Institute, Emory University School of Medicine, C-4088, 1365 C Clifton Road NE, Atlanta, Georgia 30322. fax: (404) 778-5530
    • ,
  • Hui Mao

      Affiliations

    • Department of Radiology, Emory University School of Medicine, Atlanta, Georgia
    • Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
    • ,
  • Zehong Cao

      Affiliations

    • Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
    • ,
  • Y. Andrew Wang

      Affiliations

    • Ocean Nanotech, LLC, Springdale, Arkansas
    • ,
  • Xianghong Peng

      Affiliations

    • Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
    • ,
  • Xiaoxia Wang

      Affiliations

    • Department of Radiology, Emory University School of Medicine, Atlanta, Georgia
    • ,
  • Hari K. Sajja

      Affiliations

    • Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
    • ,
  • Liya Wang

      Affiliations

    • Department of Radiology, Emory University School of Medicine, Atlanta, Georgia
    • ,
  • Hongwei Duan

      Affiliations

    • Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, Georgia
    • ,
  • Chunchun Ni

      Affiliations

    • Department of Radiology, Emory University School of Medicine, Atlanta, Georgia
    • ,
  • Charles A. Staley

      Affiliations

    • Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
    • Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
    • ,
  • William C. Wood

      Affiliations

    • Department of Surgery, Emory University School of Medicine, Atlanta, Georgia
    • Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
    • ,
  • Xiaohu Gao

      Affiliations

    • Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, Georgia
    • ,
  • Shuming Nie

      Affiliations

    • Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia
    • Department of Biomedical Engineering, Emory University School of Medicine, Atlanta, Georgia
    • Corresponding Author InformationShuming Nie, PhD, Department of Biomedical Engineering, Emory University School of Medicine, 101 Woodruff Circle, Suite 2007B, Atlanta, Georgia 30322. fax: (404) 727-3567

Received 21 February 2008 ,Accepted 8 January 2009.

References 

  1. Willett CG, Czito BG, Bendell JC, et al. Locally advanced pancreatic cancer. J Clin Oncol. 2005;23:4538–4544
  2. Weissleder R. Molecular imaging in cancer. Science. 2006;312:1168–1171
  3. Gao X, Cui Y, Levenson RM, et al. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol. 2004;22:969–976
  4. Lee JH, Huh YM, Jun YW, et al. Artificially engineered magnetic nanoparticles for ultra-sensitive molecular imaging. Nat Med. 2007;13:95–99
  5. Kelly KA, Bardeesy N, Anbazhagan R, et al. Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma. PLoS Med. 2008;5:e85
  6. Medarova Z, Pham W, Farrar C, et al. In vivo imaging of siRNA delivery and silencing in tumors. Nat Med. 2007;13:372–377
  7. Nasongkla N, Bey E, Ren J, et al. Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett. 2006;6:2427–2430
  8. Mahadevan D, Von Hoff DD. Tumor-stroma interactions in pancreatic ductal adenocarcinoma. Mol Cancer Ther. 2007;6:1186–1197
  9. Tan X, Egami H, Nozawa F, et al. Analysis of the invasion-metastasis mechanism in pancreatic cancer: involvement of plasmin(ogen) cascade proteins in the invasion of pancreatic cancer cells. Int J Oncol. 2006;28:369–374
  10. Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol. 2002;3:932–943
  11. Cantero D, Friess H, Deflorin J, et al. Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma. Br J Cancer. 1997;75:388–395
  12. Chen Y, Zheng B, Robbins DH, et al. Accurate discrimination of pancreatic ductal adenocarcinoma and chronic pancreatitis using multimarker expression data and samples obtained by minimally invasive fine needle aspiration. Int J Cancer. 2007;120:1511–1517
  13. Ploug M, Ellis V, Dano K. Ligand interaction between urokinase-type plasminogen activator and its receptor probed with 8-anilino-1-naphthalenesulfonate (Evidence for a hydrophobic binding site exposed only on the intact receptor). Biochemistry. 1994;33:8991–8997
  14. Li H, Soria C, Griscelli F, et al. Amino-terminal fragment of urokinase inhibits tumor cell invasion in vitro and in vivo: respective contribution of the urokinase plasminogen activator receptor-dependent or -independent pathway. Hum Gene Ther. 2005;16:1157–1167
  15. Bu X, Khankaldyyan V, Gonzales-Gomez I, et al. Species-specific urokinase receptor ligands reduce glioma growth and increase survival primarily by an antiangiogenesis mechanism. Lab Invest. 2004;84:667–678
  16. Rajagopal V, Kreitman RJ. Recombinant toxins that bind to the urokinase receptor are cytotoxic without requiring binding to the alpha(2)-macroglobulin receptor. J Biol Chem. 2000;275:7566–7573
  17. Choi H, Choi SR, Zhou R, et al. Iron oxide nanoparticles as magnetic resonance contrast agent for tumor imaging via folate receptor-targeted delivery. Acad Radiol. 2004;11:996–1004
  18. Yu WW, Falkner JC, Yavuz CT, et al. Synthesis of monodisperse iron oxide nanocrystals by thermal decomposition of iron carboxylate salts. Chem Commun (Camb). 2004;2306–2307
  19. Frank JA, Miller BR, Arbab AS, et al. Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. Radiology. 2003;228:480–487
  20. Ignar DM, Andrews JL, Witherspoon SM, et al. Inhibition of establishment of primary and micrometastatic tumors by a urokinase plasminogen activator receptor antagonist. Clin Exp Metastasis. 1998;16:9–20
  21. Medarova Z, Pham W, Kim Y, et al. In vivo imaging of tumor response to therapy using a dual-modality imaging strategy. Int J Cancer. 2006;118:2796–2802
  22. Pyke C, Graem N, Ralfkiaer E, et al. Receptor for urokinase is present in tumor-associated macrophages in ductal breast carcinoma. Cancer Res. 1993;53:1911–1915
  23. He Y, Liu XD, Chen ZY, et al. Interaction between cancer cells and stromal fibroblasts is required for activation of the uPAR-uPA-MMP-2 cascade in pancreatic cancer metastasis. Clin Cancer Res. 2007;13:3115–3124
  24. Graham CH, Forsdike J, Fitzgerald CJ, et al. Hypoxia-mediated stimulation of carcinoma cell invasiveness via upregulation of urokinase receptor expression. Int J Cancer. 1999;80:617–623
  25. Solberg H, Ploug M, Hoyer-Hansen G, et al. The murine receptor for urokinase-type plasminogen activator is primarily expressed in tissues actively undergoing remodeling. J Histochem Cytochem. 2001;49:237–246
  26. Gupta AK, Wells S. Surface-modified superparamagnetic nanoparticles for drug delivery: preparation, characterization, and cytotoxicity studies. IEEE Trans Nanobioscience. 2004;3:66–73
  27. Stahl A, Mueller BM. The urokinase-type plasminogen activator receptor, a GPI-linked protein, is localized in caveolae. J Cell Biol. 1995;129:335–344
  28. Oh P, Borgstrom P, Witkiewicz H, et al. Live dynamic imaging of caveolae pumping targeted antibody rapidly and specifically across endothelium in the lung. Nat Biotechnol. 2007;25:327–337

 Conflicts of interest Y.A.W. discloses that he is the president and principal scientist of Ocean Nanotech LLC. The remaining authors disclose no conflicts.

 Funding Supported by the Emory-Georgia Tech Nanotechnology Center for Personalized and Predictive Oncology of the National Institutes of Health Center of Cancer Nanotechnology Excellence (CCNE, U54 CA119338-01) and by seed grants from the Golfers Against Cancer Foundation, The Friends For An Early Breast Cancer Test, and EmTech Bio, Inc.

PII: S0016-5085(09)00012-2

doi: 10.1053/j.gastro.2009.01.006

Gastroenterology
Volume 136, Issue 5 , Pages 1514-1525.e2 , May 2009

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