Positron Emission Tomography and Near-Infrared Fluorescence Imaging of Vascular Endothelial Growth Factor with Dual-Labeled Bevacizumab.

摘要: The pivotal role of vascular endothelial growth factor (VEGF) in cancer is underscored by the approval bevacizumab (Bev, a humanized anti-VEGF monoclonal antibody) for first line treatment patients. aim this study was to develop dual-labeled Bev both positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging VEGF. conjugated NIRF dye (i.e. 800CW) 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) before (64)Cu-labeling. Flow cytometry analysis U87MG human glioblastoma cells revealed no difference VEGF binding affinity/specificity between NOTA-Bev-800CW. (64)Cu-labeling NOTA-Bev-800CW achieved with high yield. Serial PET tumor-bearing female nude mice that tumor uptake (64)Cu-NOTA-Bev-800CW 4.6 ± 0.7, 16.3 1.6, 18.1 1.4 20.7 3.7 %ID/g at 4, 24, 48 72 h post-injection respectively (n = 4), corroborated vivo/ex vivo biodistribution studies. Tumor as measured ex had good linear correlation values obtained from (R(2) 0.93). Blocking experiments histology confirmed specificity (64)Cu-NOTA-Bev-800CW. persistent, prominent, VEGF-specific tumor, observed imaging, warrants further investigation future clinical translation such Bev-based agents.