caa a22 4500 445795697 CHVBK 20180317145124.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s10620-011-1685-z doi (NATIONALLICENCE)springer-10.1007/s10620-011-1685-z Application of Near-Infrared Fluorescence Imaging Using a Polymeric Nanoparticle-Based Probe for the Diagnosis and Therapeutic Monitoring of Colon Cancer [Elektronische Daten] [Soon Yoon, Seung-Jae Myung, In-Wha Kim, Eun-Ju Do, Byong Ye, Ju Ryu, Kyeongsoon Park, Kwangmeyung Kim, Ick Kwon, Mi Kim, Dae Moon, Dong-Hoon Yang, Kyoung Kim, Jeong-Sik Byeon, Suk-Kyun Yang, Jin-Ho Kim] Background: Early and accurate detection of adenomatous colonic polyps is a major concern in the prevention of colon cancer. Near-infrared fluorescence (NIRF) imaging with optical probes targeting specific peptides enables the noninvasive visualization and characterization of lesions. Matrix metalloproteinases (MMPs) are known to play an important role in tumorigenesis and tumor progression. Aim: To investigate the effectiveness of NIRF imaging, with a novel MMP-activatable probe based on a polymeric nanoparticle platform, in the colon cancer models. Methods: We used an azoxymethane (AOM)-induced mouse colon cancer model resembling human sporadic colon cancer and an MMP-positive xenograft tumor model. MMP expression was evaluated by Western blotting, real-time PCR, and immunohistochemical staining. NIRF imaging was performed with a novel MMP-activatable probe, an MMP-inactivatable probe, and saline. In addition, we observed the change of NIRF signal intensity after intratumoral administration of an MMP-inhibitor. Results: Multiple tumors with various sizes developed in AOM-treated mouse colons, progressing from adenomas to adenocarcinomas, with MMP expression progressively increasing in the normal-adenoma-adenocarcinoma sequence. In mice injected with the MMP-activatable probe, the NIRF signal also increased in this sequence and was highly correlated with MMP expression (p<0.001). Tumor-background-ratios (TBR) of adenocarcinoma to adjacent normal mucosa by a novel probe were significantly higher than that of adenoma (p<0.001). In both the AOM and xenograft models, NIRF signals of tumors decreased after treatment with an MMP-inhibitor. Conclusions: NIRF imaging using a polymeric nanoparticle-based probe may be useful for detecting early stage disease and for assessing treatment response. Springer Science+Business Media, LLC, 2011 Colon cancer nationallicence Near-infrared fluorescence nationallicence Nanoparticles nationallicence Matrix metalloproteinases nationallicence Yoon Soon Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea aut Myung Seung-Jae Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut Kim In-Wha Molecular Imaging Center, Asan Institute for Life Sciences, Seoul, Korea aut Do Eun-Ju Molecular Imaging Center, Asan Institute for Life Sciences, Seoul, Korea aut Ye Byong Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut Ryu Ju Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea aut Park Kyeongsoon Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea aut Kim Kwangmeyung Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea aut Kwon Ick Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea aut Kim Mi Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea aut Moon Dae Molecular Imaging Center, Asan Institute for Life Sciences, Seoul, Korea aut Yang Dong-Hoon Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut Kim Kyoung Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut Byeon Jeong-Sik Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut Yang Suk-Kyun Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut Kim Jin-Ho Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut Digestive Diseases and Sciences Springer US; http://www.springer-ny.com 56/10(2011-10-01), 3005-3013 0163-2116 56:10<3005 2011 56 10620 https://doi.org/10.1007/s10620-011-1685-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10620-011-1685-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yoon Soon Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea aut NATIONALLICENCE 700 1- Myung Seung-Jae Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut NATIONALLICENCE 700 1- Kim In-Wha Molecular Imaging Center, Asan Institute for Life Sciences, Seoul, Korea aut NATIONALLICENCE 700 1- Do Eun-Ju Molecular Imaging Center, Asan Institute for Life Sciences, Seoul, Korea aut NATIONALLICENCE 700 1- Ye Byong Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut NATIONALLICENCE 700 1- Ryu Ju Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea aut NATIONALLICENCE 700 1- Park Kyeongsoon Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea aut NATIONALLICENCE 700 1- Kim Kwangmeyung Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea aut NATIONALLICENCE 700 1- Kwon Ick Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea aut NATIONALLICENCE 700 1- Kim Mi Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea aut NATIONALLICENCE 700 1- Moon Dae Molecular Imaging Center, Asan Institute for Life Sciences, Seoul, Korea aut NATIONALLICENCE 700 1- Yang Dong-Hoon Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut NATIONALLICENCE 700 1- Kim Kyoung Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut NATIONALLICENCE 700 1- Byeon Jeong-Sik Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut NATIONALLICENCE 700 1- Yang Suk-Kyun Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut NATIONALLICENCE 700 1- Kim Jin-Ho Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap, 2 dong, Songpa-gu, 138-736, Seoul, Korea aut NATIONALLICENCE 773 0- Digestive Diseases and Sciences Springer US; 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