10.1021/bc500415x.s001 Rubel Chakravarty Rubel Chakravarty Shreya Goel Shreya Goel Hector F. Valdovinos Hector F. Valdovinos Reinier Hernandez Reinier Hernandez Hao Hong Hao Hong Robert J. Nickles Robert J. Nickles Weibo Cai Weibo Cai Matching the Decay Half-Life with the Biological Half-Life: ImmunoPET Imaging with <sup>44</sup>Sc-Labeled Cetuximab Fab Fragment American Chemical Society 2015 Fab uptake EGFR expression PET imaging epidermal growth factor receptor positron emission tomography tumor 87MG 44 Sc 4 h postinjection day PET imaging vivo PET imaging ID Cetuximab 2015-12-17 06:25:45 Journal contribution https://acs.figshare.com/articles/journal_contribution/Matching_the_Decay_Half_Life_with_the_Biological_Half_Life_ImmunoPET_Imaging_with_sup_44_sup_Sc_Labeled_Cetuximab_Fab_Fragment/2045652 Scandium-44 (<i>t</i><sub>1/2</sub> = 3.9 h) is a relatively new radioisotope of potential interest for use in clinical positron emission tomography (PET). Herein, we report, for the first time, the room-temperature radiolabeling of proteins with <sup>44</sup>Sc for <i>in vivo</i> PET imaging. For this purpose, the Fab fragment of Cetuximab, a monoclonal antibody that binds with high affinity to epidermal growth factor receptor (EGFR), was generated and conjugated with <i>N</i>-[(R<i>)</i>-2-amino-3-(<i>para</i>-isothiocyanato-phenyl)­propyl]-<i>trans</i>-(<i>S</i>,<i>S</i>)-cyclohexane-1,2-diamine-<i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>″,<i>N</i>″-pentaacetic acid (CHX-A″-DTPA). The high purity of Cetuximab-Fab was confirmed by SDS-PAGE and mass spectrometry. The potential of the bioconjugate for PET imaging of EGFR expression in human glioblastoma (U87MG) tumor-bearing mice was investigated after <sup>44</sup>Sc labeling. PET imaging revealed rapid tumor uptake (maximum uptake of ∼12% ID/g at 4 h postinjection) of <sup>44</sup>Sc–CHX-A″-DTPA–Cetuximab-Fab with excellent tumor-to-background ratio, which might allow for same day PET imaging in future clinical studies. Immunofluorescence staining was conducted to correlate tracer uptake in the tumor and normal tissues with EGFR expression. This successful strategy for immunoPET imaging of EGFR expression using <sup>44</sup>Sc–CHX-A″-DTPA–Cetuximab-Fab can make clinically translatable advances to select the right population of patients for EGFR-targeted therapy and also to monitor the therapeutic efficacy of anti-EGFR treatments.