Intraoperative Near-Infrared Fluorescence Tumor Imaging with Vascular Endothelial Growth Factor and Human Epidermal Growth Factor Receptor 2 Targeting Antibodies

Journal of Nuclear Medicine

Harry Hollema¹  Marjolijn N. Lub-de Hoog¹  Wouter B. Nagengast¹  Anton G.T. Terwisscha van Scheltinga¹  Vasilis Ntziachristos¹  Gooitzen M. van Dam¹  Jos G.W. Kosterink¹  Elisabeth G.E. de Vries¹  Carolien P. Schröder¹  Jennifer L. Herek¹ 

关键词: molecular imaging;    monoclonal antibodies;    oncology;    intraoperative imaging;    near-infrared fluorescence;   

DOI  :  10.2967/jnumed.111.092833

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

Fluorescence imaging is currently attracting much interest as a method for intraoperative tumor detection, but most current tracers lack tumor specificity. Therefore, this technique can be further improved by tumor-specific detection. With tumor-targeted antibodies bound to a radioactive label, tumor-specific SPECT or PET is feasible in the clinical setting. The aim of the present study was to apply antibody-based tumor detection to intraoperative optical imaging, using preclinical in vivo mouse models. Methods: Anti–vascular endothelial growth factor (VEGF) antibody bevacizumab and anti–human epidermal growth factor receptor (HER) 2 antibody trastuzumab were labeled with the near-infrared (NIR) fluorescence dye IRDye 800CW. Tumor uptake of the fluorescent tracers and their 89Zr-labeled radioactive counterparts for PET was determined in human xenograft–bearing athymic mice during 1 wk after tracer injection, followed by ex vivo biodistribution and pathologic examination. Intraoperative imaging of fluorescent VEGF- or HER2-positive tumor lesions was performed in subcutaneous tumors and in intraperitoneal dissemination tumor models. Results: Tumor-to-background ratios, with fluorescent imaging, were 1.93 ± 0.40 for bevacizumab and 2.92 ± 0.29 for trastuzumab on day 6 after tracer injection. Real-time intraoperative imaging detected tumor lesions at even the submillimeter level in intraperitoneal dissemination tumor models. These results were supported by standard histology, immunohistochemistry, and fluorescence microscopy analyses. Conclusion: NIR fluorescence–labeled antibodies targeting VEGF or HER2 can be used for highly specific and sensitive detection of tumor lesions in vivo. These preclinical findings encourage future clinical studies with NIR fluorescence–labeled tumor-specific antibodies for intraoperative-guided surgery in cancer patients.

【 授权许可】

Unknown