TY - JOUR
T1 - Novel human monoclonal antibody against epidermal growth factor receptor as an imaging probe for hepatocellular carcinoma
AU - Sogawa, Chizuru
AU - Tsuji, Atsushi B.
AU - Yoshida, Chisato
AU - Inubushi, Masayuki
AU - Furukawa, Takako
AU - Koizumi, Mitsuru
AU - Akahori, Yasushi
AU - Ukai, Yoshinori
AU - Kurosawa, Gene
AU - Kurosawa, Yoshikazu
AU - Saga, Tsuneo
PY - 2012/7
Y1 - 2012/7
N2 - 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.
AB - 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.
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U2 - 10.1097/MNM.0b013e3283531d68
DO - 10.1097/MNM.0b013e3283531d68
M3 - Article
C2 - 22453549
AN - SCOPUS:84862234784
VL - 33
SP - 719
EP - 725
JO - Nuclear Medicine Communications
JF - Nuclear Medicine Communications
SN - 0143-3636
IS - 7
ER -