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

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 111 indium (111 In) in this study for diagnosing EGFR-positive CRC. The aim of this study was to evaluate the efficacy of noninvasive nuclear imaging agent 111 In-cetuximab and investigate the biological distribution of 111 In-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 111 In and measured the labeling efficacy by an instant thin layer chromatography (iTLC). Furthermore, the 111 In-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 111 In was calculated and experimented as 48 μg, resulting in labeling efficacy >80% detected by iTLC. The results revealed that the 111 In-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 111 In-cetuximab bound to tumor specifically that was higher than that in other organs.

CONCLUSION: We suggested that the 111 In-cetuximab was potential for early diagnosis and prognostic monitor of EGFR-positive CRC in further clinical practice.