On the Selection of a Tracer for PET Imaging of HER2-Expressing Tumors: Direct Comparison of a 124I-Labeled Affibody Molecule and Trastuzumab in a Murine

Human epidermal growth factor receptor type 2 (HER2) is a tyro-sine kinase, which is often overexpressed in many carcinomas. Imaging HER2 expression in malignant tumors can provide im-portant prognostic and predictive diagnostic information. The use of anti-HER2 tracers labeled with positron-emitting radionu-clides may increase the sensitivity of HER2 imaging. The goal of this study was to compare directly 2 approaches for developing anti-HER2PET tracers: a 124I-labeledmonoclonal antibody and a small (7-kDa) scaffold protein, the Affibody molecule. Methods: The anti-HER2 Affibody ZHER2:342 and humanized monoclonal antibody trastuzumab were labeled with 124/125I using p-iodo-benzoate (PIB) as a linker. Cellular processing of both tracers by HER2-expressing cells was investigated. The biodistributions of 124I-PIB-ZHER2:342 and 125I-PIB-trastuzumab were compared in BALB/C nu/numice bearing HER2-expressing NCI-N87 xeno