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Epidermal growth factor receptor-targeted molecular imaging of colorectal tumors: Detection and treatment evaluation of tumors in animal models.

Abstract
To overcome the problem of overlooking colorectal tumors, a new and highly sensitive modality of colonoscopy is needed. Moreover, it is also important to establish a new modality to evaluate viable tumor volume in primary lesions of colorectal cancer (CRC) during chemotherapy. Therefore, we carried out molecular imaging of colorectal tumors targeting epidermal growth factor receptor (EGFR), which is highly expressed on tumor cells, for evaluating chemotherapeutic efficacy and for endoscopic detection of colorectal adenomas. We first attempted to image five CRC cell lines with various levels of EGFR expression using an Alexa Fluor-labeled anti-EGFR monoclonal antibody (AF-EGFR-Ab). A strong fluorescence signal was observed in the cells depending on the level of EGFR expression. When nude mice xenografted with LIM1215 CRC cells, which highly express EGFR, were i.v. injected with AF-EGFR-Ab, a strong fluorescence signal appeared in the tumor with a high signal to noise ratio, peaking at 48 hours after injection and then gradually decreasing, as shown using an IVIS Spectrum system. When the xenografted mice were treated with 5-fluorouracil, fluorescence intensity in the tumor decreased in proportion to the viable tumor cell volume. Moreover, when the colorectum of azoxymethane-treated rats was observed using a thin fluorescent endoscope with AF-EGFR-Ab, all 10 small colorectal adenomas (≤3 mm) were detected with a clear fluorescence signal. These preliminary results of animal experiments suggest that EGFR-targeted fluorescent molecular imaging may be useful for quantitatively evaluating cell viability in CRC during chemotherapy, and also for detecting small adenomas using a fluorescent endoscope.
AuthorsYoshihiko Miyamoto, Naoki Muguruma, Shota Fujimoto, Yasuyuki Okada, Yoshifumi Kida, Fumika Nakamura, Kumiko Tanaka, Tadahiko Nakagawa, Shinji Kitamura, Koichi Okamoto, Hiroshi Miyamoto, Yasushi Sato, Tetsuji Takayama
JournalCancer science (Cancer Sci) Vol. 110 Issue 6 Pg. 1921-1930 (Jun 2019) ISSN: 1349-7006 [Electronic] England
PMID30973663 (Publication Type: Journal Article)
Copyright© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Chemical References
  • Antineoplastic Agents
  • ErbB Receptors
  • Azoxymethane
  • Fluorouracil
Topics
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Azoxymethane (pharmacology)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Colorectal Neoplasms (diagnostic imaging, drug therapy, metabolism)
  • ErbB Receptors (antagonists & inhibitors, metabolism)
  • Female
  • Fluorouracil (pharmacology)
  • HT29 Cells
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Targeted Therapy (methods)
  • Rats, Inbred F344
  • Xenograft Model Antitumor Assays

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