SPECT imaging evaluation of 111indium-chelated cetuximab for diagnosing EGFR-positive tumor in an HCT-15-induced colorectal xenograft

Bin Bin Shih, Yi Fang Chang, Chun Chia Cheng, Hao Jhih Yang, Kang Wei Chang, Ai Sheng Ho, Hua Ching Lin, Chun Yeh, Chun Chao Chang

研究成果: 雜誌貢獻文章

7 引文 斯高帕斯(Scopus)

摘要

Background: Epidermal growth factor receptor (EGFR) overexpressed in colorectal cancer (CRC) is a tumor target for developing the anti-tumor theranostic agents. Cetuximab, an anti-EGFR monoclonal antibody against EGFR-positive tumors, inhibits cell proliferation and growth was labeled with radioactive 111indium (111In) in this study for diagnosing EGFR-positive CRC. The aim of this study was to evaluate the efficacy of noninvasive nuclear imaging agent 111In-cetuximab and investigate the biological distribution of 111In-cetuximab in the HCT-15-induced EGFR-positive CRC tumor xenografts. Methods: We conjugated cetuximab with an isotope chelator, diethylene triamine penta acetic acid (DTPA), and consequently labeled cetuximab-DTPA with 111In and measured the labeling efficacy by an instant thin layer chromatography (iTLC). Furthermore, the 111In-cetuximab was investigated and compared for imaging small (50 mm3) and large (250 mm3) tumor of CRC xenografts, respectively. Results: The conjugated ratio between cetuximab and DTPA was 1:6 measured by MALDI-TOF-MS. The better labeling concentration of cetuximab with 10 mCi of 111In was calculated and experimented as 48 μg, resulting in labeling efficacy >80% detected by iTLC. The results revealed that the 111In-cetuximab accumulated in the both sizes of tumors as a reliable noninvasive diagnostic agent, whereas the ratio of tumor to muscle in the large tumor was 7.5-fold. The biodistribution data indicated that the 111In-cetuximab bound to tumor specifically that was higher than that in other organs. Conclusion: We suggested that the 111In-cetuximab was potential for early diagnosis and prognostic monitor of EGFR-positive CRC in further clinical practice.

ASJC Scopus subject areas

  • Medicine(all)

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