PT - JOURNAL ARTICLE AU - Martin Eiblmaier AU - Laura A. Meyer AU - Mark A. Watson AU - Paula M. Fracasso AU - Linda J. Pike AU - Carolyn J. Anderson TI - Correlating EGFR Expression with Receptor-Binding Properties and Internalization of <sup>64</sup>Cu-DOTA-Cetuximab in 5 Cervical Cancer Cell Lines AID - 10.2967/jnumed.108.052316 DP - 2008 Sep 01 TA - Journal of Nuclear Medicine PG - 1472--1479 VI - 49 IP - 9 4099 - http://jnm.snmjournals.org/content/49/9/1472.short 4100 - http://jnm.snmjournals.org/content/49/9/1472.full SO - J Nucl Med2008 Sep 01; 49 AB - 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 &gt; ME-180 &gt; DoTc2 4510 &gt; HeLa &gt; 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.