Digestive Diseases and Sciences

, Volume 56, Issue 10, pp 3005–3013

Application of Near-Infrared Fluorescence Imaging Using a Polymeric Nanoparticle-Based Probe for the Diagnosis and Therapeutic Monitoring of Colon Cancer

  • Soon Man Yoon
  • Seung-Jae Myung
  • In-Wha Kim
  • Eun-Ju Do
  • Byong Duk Ye
  • Ju Hee Ryu
  • Kyeongsoon Park
  • Kwangmeyung Kim
  • Ick Chan Kwon
  • Mi Jung Kim
  • Dae Hyuk Moon
  • Dong-Hoon Yang
  • Kyoung Jo Kim
  • Jeong-Sik Byeon
  • Suk-Kyun Yang
  • Jin-Ho Kim
Original Article

DOI: 10.1007/s10620-011-1685-z

Cite this article as:
Yoon, S.M., Myung, SJ., Kim, IW. et al. Dig Dis Sci (2011) 56: 3005. doi:10.1007/s10620-011-1685-z

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.

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.

Keywords

Colon cancer Near-infrared fluorescence Nanoparticles Matrix metalloproteinases 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Soon Man Yoon
    • 1
  • Seung-Jae Myung
    • 2
    • 3
  • In-Wha Kim
    • 3
  • Eun-Ju Do
    • 3
  • Byong Duk Ye
    • 2
    • 3
  • Ju Hee Ryu
    • 4
  • Kyeongsoon Park
    • 4
  • Kwangmeyung Kim
    • 4
  • Ick Chan Kwon
    • 4
  • Mi Jung Kim
    • 5
  • Dae Hyuk Moon
    • 3
    • 6
  • Dong-Hoon Yang
    • 2
  • Kyoung Jo Kim
    • 2
  • Jeong-Sik Byeon
    • 2
  • Suk-Kyun Yang
    • 2
  • Jin-Ho Kim
    • 2
  1. 1.Department of Internal MedicineChungbuk National University College of MedicineCheongjuKorea
  2. 2.Department of Internal Medicine, Asan Digestive Disease Research Institute, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  3. 3.Molecular Imaging CenterAsan Institute for Life SciencesSeoulKorea
  4. 4.Biomedical Research CenterKorea Institute of Science and TechnologySeoulKorea
  5. 5.Department of Pathology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  6. 6.Department of Nuclear Medicine, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea