Matching the Decay Half-Life with the Biological Half-Life: ImmunoPET Imaging with 44Sc-Labeled Cetuximab Fab Fragment

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• 作者：Rubel Chakravarty ; Shreya Goel ; Hector F. Valdovinos ; Reinier Hernandez ; Hao Hong ; Robert J. Nickles ; Weibo Cai
• 刊名：Bioconjugate Chemistry
• 出版年：2014
• 出版时间：December 17, 2014
• 年：2014
• 卷：25
• 期：12
• 页码：2197-2204
• 全文大小：409K
• ISSN：1520-4812

文摘

Scandium-44 (t_1/2 = 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 ⁴⁴Sc for in vivo 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 N-[(R)-2-amino-3-(para-isothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N鈥?N鈥?N鈥?pentaacetic acid (CHX-A鈥?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 ⁴⁴Sc labeling. PET imaging revealed rapid tumor uptake (maximum uptake of 鈭?2% ID/g at 4 h postinjection) of ⁴⁴Sc鈥揅HX-A鈥?DTPA鈥揅etuximab-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 ⁴⁴Sc鈥揅HX-A鈥?DTPA鈥揅etuximab-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.