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Basic Science Investigation |
1 Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri; 2 Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri; 3 Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; 4 Department of Biochemistry, Washington University School of Medicine, St. Louis, Missouri; and 5 Department of Chemistry, Washington University School of Medicine, St. Louis, Missouri
Correspondence: For correspondence or reprints contact: Carolyn J. Anderson, Mallinckrodt Institute of Radiology, 510 S. Kingshighway Blvd., Campus Box 8225, St. Louis, MO 63110. E-mail: andersoncj{at}wustl.edu
The anti–epidermal growth factor receptor (anti-EGFR) antibody cetuximab is clinically approved for the treatment of EGFR-expressing metastatic colorectal cancer and advanced head and neck cancer. Overexpression of EGFR has also been found in more than 70% of carcinomas of the cervix. The overall goal of this study was to determine whether 64Cu-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-cetuximab has potential as an agent for measuring EGFR concentration by PET imaging in cervical cancer tumors. Methods: Cetuximab was conjugated to the bifunctional chelator DOTA and labeled with 64Cu. EGFR messenger RNA (mRNA) expression was correlated with EGFR densities on the cell surface of 5 different cervical cancer cell lines and with receptor function, measured by internalization of 64Cu-DOTA-cetuximab. Imaging in tumor-bearing mice with small-animal PET was performed using the highest-expressing cervical cancer cell line. Results: The affinity of 64Cu-DOTA-cetuximab binding for the EGFR was similar in 4 EGFR-positive lines, varying from 0.1 to 0.7 nM. The mRNA expression corresponded well with EGFR densities and levels of internalization, with responses decreasing in the order of CaSki > ME-180 > DoTc2 4510 > HeLa > C-33A. Biodistribution and small-animal PET studies with 64Cu-DOTA-cetuximab in CaSki tumor-bearing nude mice showed relatively high tumor uptake at 24 h after injection (13.2 ± 1.2 percentage of injected activity per gram), although there was also significant retention of activity in the blood and liver accumulation. Conclusion: 64Cu-DOTA-cetuximab was successfully used to detect and quantify EGFR expression in cervical cancer tumors, and small-animal PET/CT of EGFR-expressing CaSki tumors suggests potential for PET/CT of EGFR-positive tumors.
Key Words: 64Cu cervical cancer cetuximab
COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.
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