Novel human monoclonal antibody against epidermal growth factor receptor as an imaging probe for hepatocellular carcinoma

OBJECTIVE: The epidermal growth factor receptor (EGFR) is overexpressed in many epithelial cancers, including hepatocellular carcinoma (HCC), and is an attractive target for cancer imaging and therapy. We attempted a novel noninvasive imaging method to evaluate anti-EGFR human monoclonal antibody clones for determining the uptake of therapeutic anti-EGFR antibody in HCC. METHODS: In-vitro cell binding of nine ¹²⁵I-labeled antibody clones was compared in the human epidermoid cancer cell line A431, in three HCC cell lines Hep-G2, SK-Hep1, and HuH-7, and in the EGFR-negative control cell line A4. ¹¹¹In-labeled or ¹²⁵I-labeled 048-006 was subjected to cell binding, competitive inhibition, and internalization assays using A431, SK-Hep1, and HuH-7. Further, ¹¹¹In-labeled 048-006 was evaluated in in-vivo biodistribution analysis and single-photon imaging in nude tumor-bearing mice. RESULTS: The 048-006 clone showed the highest binding to EGFR-expressing cells among the nine antibodies. ¹¹¹In-labeled or ¹²⁵I-labeled 048-006 specifically bound to EGFR-expressing cells with high affinity and was internalized after binding to EGFR. A431 and HuH-7 tumors showed high ¹¹¹In-labeled 048-006 uptake, which was visualized by single-photon imaging. CONCLUSION: Radiolabeled human anti-EGFR monoclonal antibody 048-006 has the potential to be a safer imaging probe for predicting tumor uptake of anti-EGFR antibody therapeutic agents in HCC.