111In-cetuximab as a diagnostic agent by accessible epidermal growth factor (EGF) receptor targeting in human metastatic colorectal carcinoma

Oncotarget. 2015 Jun 30;6(18):16601-10. doi: 10.18632/oncotarget.3968.

Abstract

Colorectal adenocarcinoma is a common cause death cancer in the whole world. The aim of this study is to define the 111In-cetuximab as a diagnosis tracer of human colorectal adenocarcinoma. In this research, cell uptake, nano-SPECT/CT scintigraphy, autoradiography, biodistribution and immunohitochemical staining of EGF receptor were included. HCT-116 and HT-29 cell expressed a relatively high and moderate level of EGF receptor, respectively. The nano-SPECT/CT image of 111In-cetuximab showed tumor radiation uptake of subcutaneous HCT-116 xenograft tumor was higher than SW-620. Autoradiography image also showed that tumor of HCT-116 had high 111In-cetuximab uptake. Mice that bearing CT-26 in situ xenograft colorectal tumors showed similar high uptake in vivo and ex vivo through nano-SPECT/CT imaging at 72 hours. Metastatic HCT-116/Luc tumors demonstrated the highest uptake at 72 hours after the injection of 111In-cetuximab. Relatively, results of 111In-DTPA showed that metabolism through urinary system, especially in the kidney. The quantitative analysis of biodistribution showed count value of metastatic HCT-116/Luc tumors that treated with 111In-cetuximab had a significant difference (P < 0.05) compared with that treated with 111In-DTPA after injection 72 hours. Result of immunohistologic staining of EGF receptor also showed high EGF receptor expression and uptake in metastatic colorectal tumors. In summary, we suggested that 111In-cetuximab will be a potential tool for detecting EGF receptor expression in human metastatic colorectal carcinoma.

Keywords: EGF receptor; cetuximab; colorectal adenocarcinoma; nano-SPECT/CT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis*
  • Adenocarcinoma / diagnostic imaging
  • Animals
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Biological Transport / physiology
  • Cell Line, Tumor
  • Cetuximab / pharmacology*
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / diagnostic imaging*
  • ErbB Receptors / metabolism*
  • HCT116 Cells
  • HT29 Cells
  • Heterografts
  • Humans
  • Indium Radioisotopes
  • Kidney / metabolism
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis / diagnostic imaging
  • Neoplasm Transplantation
  • Radiography
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Antineoplastic Agents
  • Indium Radioisotopes
  • EGFR protein, human
  • ErbB Receptors
  • Cetuximab