Imaging of Epidermal Growth Factor Receptor Expression in Head and Neck Cancer with USPECT and 111In-Labeled Cetuximab-F(ab9)2

Combined treatment of advanced head and neck squamous cell carcinomas (HNSCC) with radiotherapy and the epidermal growth factor receptor (EGFR) inhibitor cetuximab improves clinical out-come in comparison to radiotherapy alone but is only effective in a few cases. To select those patients most likely to benefit from EGFR inhibition, it can be advantageous to quantify the tumor EGFR status before and possibly during therapy. The aim of this study was to develop and characterize the 111In-cetuximab-F(ab9)2 tracer to image EGFR targeting in vivo. Methods: The affinity and internali-zation kinetics of 111In-cetuximab-F(ab9)2 were determined in vitro. The optimal protein-fragment dose for imaging was determined in nude mice with a subcutaneous head and neck carcinoma model (FaDu). Mice with FaDu tumors were imaged using ultra-high-reso-lution SPECT (USPECT) with 111In-cetuximab-F(ab9)2 or 111In-cetux-imab IgG at 4, 24, 48, and 168 h after injection. Tumor tracer uptak