title: Application of near-infrared fluorescence imaging using a polymeric nanoparticle-based probe for the diagnosis and therapeutic monitoring of colon cancer.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea.
authors.forename: Soon Man
authors.initials: SM
authors.lastname: Yoon
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Myung
authors.forename: In-Wha
authors.initials: IW
authors.lastname: Kim
authors.forename: Eun-Ju
authors.initials: EJ
authors.lastname: Do
authors.forename: Byong Duk
authors.initials: BD
authors.lastname: Ye
authors.forename: Ju Hee
authors.initials: JH
authors.lastname: Ryu
authors.forename: Kyeongsoon
authors.initials: K
authors.lastname: Park
authors.forename: Kwangmeyung
authors.initials: K
authors.lastname: Kim
authors.forename: Ick Chan
authors.initials: IC
authors.lastname: Kwon
authors.forename: Mi Jung
authors.initials: MJ
authors.lastname: Kim
authors.forename: Dae Hyuk
authors.initials: DH
authors.lastname: Moon
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Yang
authors.forename: Kyoung Jo
authors.initials: KJ
authors.lastname: Kim
authors.forename: Jeong-Sik
authors.initials: JS
authors.lastname: Byeon
authors.forename: Suk-Kyun
authors.initials: SK
authors.lastname: Yang
authors.forename: Jin-Ho
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced / Q000175:diagnosis* / Q000188:drug therapy*; D000818:Animals; D001397:Azoxymethane / Q000009:adverse effects; D045744:Cell Line, Tumor; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000175:diagnosis* / Q000188:drug therapy*; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D018450:Disease Progression; D004358:Drug Therapy; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005456:Fluorescent Dyes; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008815:Mice, Inbred Strains; D053758:Nanoparticles; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D061965:Matrix Metalloproteinase Inhibitors; D020783:Matrix Metalloproteinase 7; D001397:Azoxymethane