Application of Near-Infrared Fluorescence Imaging Using a Polymeric Nanoparticle-Based Probe for the Diagnosis and Therapeutic Monitoring of Colon Cancer
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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.
To investigate the effectiveness of NIRF imaging, with a novel MMP-activatable probe based on a polymeric nanoparticle platform, in the colon cancer models.
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.
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.
NIRF imaging using a polymeric nanoparticle-based probe may be useful for detecting early stage disease and for assessing treatment response.
- Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–249. CrossRef
- Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer. CA Cancer J Clin. 2009;59:366–378. CrossRef
- Vogelstein B, Fearon ER, Hamilton SR, et al. Genetic alterations during colorectal-tumor development. N Engl J Med. 1988;319:525–532. CrossRef
- Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med. 1993;329:1977–1981. CrossRef
- Rex DK, Cutler CS, Lemmel GT, et al. Colonoscopic miss rates of adenomas determined by back-to-back colonoscopies. Gastroenterology. 1997;112:24–28. CrossRef
- Rembacken BJ, Fujii T, Cairns A, et al. Flat and depressed colonic neoplasms: a prospective study of 1000 colonoscopies in the UK. Lancet. 2000;355:1211–1214. CrossRef
- Fennerty MB. Tissue staining (chromoscopy) of the gastrointestinal tract. Can J Gastroenterol. 1999;13:423–429.
- Machida H, Sano Y, Hamamoto Y, et al. Narrow-band imaging in the diagnosis of colorectal mucosal lesions: a pilot study. Endoscopy. 2004;36:1094–1098. CrossRef
- Weissleder R, Ntziachristos V. Shedding light onto live molecular targets. Nat Med. 2003;9:123–128. CrossRef
- Weissleder R. Molecular imaging in cancer. Science. 2006;312:1168–1171. CrossRef
- Mahmood U, Wallace MB. Molecular imaging in gastrointestinal disease. Gastroenterology. 2007;132:11–14. CrossRef
- Weissleder R, Mahmood U. Molecular imaging. Radiology. 2001;219:316–333.
- Hilderbrand SA, Weissleder R. Near-infrared fluorescence: application to in vivo molecular imaging. Curr Opin Chem Biol. 2010;14:71–79. CrossRef
- Lee S, Park K, Kim K, Choi K, Kwon IC. Activatable imaging probes with amplified fluorescent signals. Chem Commun (Camb). 2008:4250–4260.
- Yang Z, Leon J, Martin M, et al. Pharmacokinetics and biodistribution of near-infrared fluorescence polymeric nanoparticles. Nanotechnology. 2009;20:165101. CrossRef
- Lee S, Ryu JH, Park K, et al. Polymeric nanoparticle-based activatable near-infrared nanosensor for protease determination in vivo. Nano Lett. 2009;9:4412–4416. CrossRef
- Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science. 2002;295:2387–2392. CrossRef
- Mysliwiec AG, Ornstein DL. Matrix metalloproteinases in colorectal cancer. Clin Colorectal Cancer. 2002;1:208–219. CrossRef
- Kirimlioglu H, Kirimlioglu V, Yilmaz S, et al. Role of matrix metalloproteinase-7 in colorectal adenomas. Dig Dis Sci. 2006;51:2068–2072. CrossRef
- Zucker S, Vacirca J. Role of matrix metalloproteinases (MMPs) in colorectal cancer. Cancer Metastasis Rev. 2004;23:101–117. CrossRef
- Scherer RL, McIntyre JO, Matrisian LM. Imaging matrix metalloproteinases in cancer. Cancer Metastasis Rev. 2008;27:679–690. CrossRef
- Nambiar PR, Girnun G, Lillo NA, Guda K, Whiteley HE, Rosenberg DW. Preliminary analysis of azoxymethane induced colon tumors in inbred mice commonly used as transgenic/knockout progenitors. Int J Oncol. 2003;22:145–150.
- Boivin GP, Washington K, Yang K, et al. Pathology of mouse models of intestinal cancer: consensus report and recommendations. Gastroenterology. 2003;124:762–777. CrossRef
- Turk BE, Huang LL, Piro ET, Cantley LC. Determination of protease cleavage site motifs using mixture-based oriented peptide libraries. Nat Biotechnol. 2001;19:661–667. CrossRef
- Marten K, Bremer C, Khazaie K, et al. Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice. Gastroenterology. 2002;122:406–414. CrossRef
- Brown SL, Riehl TE, Walker MR, et al. Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. J Clin Invest. 2007;117:258–269. CrossRef
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25:402–408. CrossRef
- Tung CH, Bredow S, Mahmood U, Weissleder R. Preparation of a cathepsin D sensitive near-infrared fluorescence probe for imaging. Bioconjug Chem. 1999;10:892–896. CrossRef
- Weissleder R, Tung CH, Mahmood U, Bogdanov A Jr. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol. 1999;17:375–378. CrossRef
- Portney NG, Ozkan M. Nano-oncology: drug delivery, imaging, and sensing. Anal Bioanal Chem. 2006;384:620–630. CrossRef
- Sajja HK, East MP, Mao H, Wang YA, Nie S, Yang L. Development of multifunctional nanoparticles for targeted drug delivery and noninvasive imaging of therapeutic effect. Curr Drug Discov Technol. 2009;6:43–51. CrossRef
- Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000;65:271–284. CrossRef
- Zucker S. A critical appraisal of the role of proteolytic enzymes in cancer invasion: emphasis on tumor surface proteinases. Cancer Invest. 1988;6:219–231. CrossRef
- Koblinski JE, Ahram M, Sloane BF. Unraveling the role of proteases in cancer. Clin Chim Acta. 2000;291:113–135. CrossRef
- Newell KJ, Witty JP, Rodgers WH, Matrisian LM. Expression and localization of matrix-degrading metalloproteinases during colorectal tumorigenesis. Mol Carcinog. 1994;10:199–206. CrossRef
- Bremer C, Tung CH, Weissleder R. In vivo molecular target assessment of matrix metalloproteinase inhibition. Nat Med. 2001;7:743–748. CrossRef
- Nahrendorf M, Swirski FK, Aikawa E, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 2007;204:3037–3047. CrossRef
- Application of Near-Infrared Fluorescence Imaging Using a Polymeric Nanoparticle-Based Probe for the Diagnosis and Therapeutic Monitoring of Colon Cancer
Digestive Diseases and Sciences
Volume 56, Issue 10 , pp 3005-3013
- Cover Date
- Print ISSN
- Online ISSN
- Springer US
- Additional Links
- Colon cancer
- Near-infrared fluorescence
- Matrix metalloproteinases
- Industry Sectors
- Author Affiliations
- 1. Department of Internal Medicine, Chungbuk National University College of Medicine, Cheongju, Korea
- 2. 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, Seoul, 138-736, Korea
- 3. Molecular Imaging Center, Asan Institute for Life Sciences, Seoul, Korea
- 4. Biomedical Research Center, Korea Institute of Science and Technology, Seoul, Korea
- 5. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
- 6. Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea