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A radiopharmaceutical [89Zr]Zr-DFO-nimotuzumab for immunoPET with epidermal growth factor receptor expression in vivo.

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资源类型：
Pubmed体系：
作者：
Tang Yu[1,2,3] * ; Hu Yingjiang[1] ; Liu Weihao[1] ; Chen Lin[2] ; Zhao Yan[2] ; Ma Huan[3] ; Yang Jijun[1] ; Yang Yuanyou[1] ; Liao Jiali[1] ; Cai Jiming[3] ; Chen Yue[2] ; Liu Ning[1] ;
机构： [1]Key Laboratory of Radiation Physics and Technology (Sichuan University), Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, PR China [2]Department of Nuclear Medicine, Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, PR China [3]Chengdu New Radiomedicine Technology Co. Ltd., Chengdu 610000, PR China
出处：
DOI： 10.1016/j.nucmedbio.2019.01.007
ISSN：

关键词： immunoPET EGFR [89Zr]Zr-DFO-nimotuzumab Glioma PET/CT imaging

摘要：
The potential of the positron-emitting zirconium-89 (89Zr) (t1/2 = 78.4 h) has been recently reported for immune positron emission tomography (immunoPET) radioimmunoconjugates design. In our work, we explored the optimized preparation of [89Zr]Zr-DFO-nimotuzumab, and evaluated 89Zr-labeled monoclonal antibody (mAb) construct for targeted imaging of epidermal growth factor receptor (EGFR) overexpressed in glioma. To optimize the radiolabeling efficiency of 89Zr with DFO-nimotuzumab, multiple immunoconjugates and radiolabeling were performed. Radiolabeling yield, radiochemical purity, stability, and activity assay were investigated to characterize [89Zr]Zr-DFO-nimotuzumab for chemical and biological integrity. The in vivo behavior of this tracer was studied in mice bearing subcutaneous U87MG (EGFR-positive) tumors received a 3.5 ± 0.2 MBq/dose using PET/CT imaging. One group mice bearing subcutaneous U87MG (EGFR-positive) tumors received [89Zr]Zr-DFO-nimotuzumab (3.5 ± 0.2 MBq, ~3 μg) (nonblocking) for immunoPET; the other group had 30 μg predose (blocking) of cold nimotuzumab 24 h prior to [89Zr]Zr-DFO-nimotuzumab. [89Zr]Zr-DFO-nimotuzumab was prepared with high radiochemical yield (>90%), radiochemical purity (>99%), and specific activity (115 ± 0.8 MBq/mg). In vitro validation showed that [89Zr]Zr-DFO-nimotuzumab had an initial immunoreactive fraction of 0.99 ± 0.05 and remained active for up to 5 days. A biodistribution study revealed excellent stability of [89Zr]Zr-DFO-nimotuzumab in vivo compared with 89Zr as a bone seeker. High uptake in the liver and heart and modest penetration in the brain were observed, with no significant accumulation of activity in other organs. ImmunoPET studies also indicated prominent image contrast that remarkably high uptake up to ~20%ID/g for nonblocking and ~2%ID/g for blocking in tumor between 12 and 120 h after administration. These studies developed a radiopharmaceutical [89Zr]Zr-DFO-nimotuzumab with optimized synthesis. The potential utility of [89Zr]Zr-DFO-nimotuzumab in assessing EGFR status in glioma was demonstrated in this study. Copyright © 2019 Elsevier Inc. All rights reserved.

基金：
the Key Research Development Project of Sichuan Provincial Department of Science and Technology (2018SZ0022), Strategic Cooperation Project of Luzhou Municipal People's Government of Sichuan University, China (2018CDLZ-09) and the Open Program of Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2019]版：
大类 | 3 区 医学
小类 | 3 区 核医学
最新[2023]版：
大类 | 4 区 医学
小类 | 4 区 核医学
第一作者：
第一作者机构： [1]Key Laboratory of Radiation Physics and Technology (Sichuan University), Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, PR China [2]Department of Nuclear Medicine, Hospital of Southwest Medical University, Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou 646000, PR China [3]Chengdu New Radiomedicine Technology Co. Ltd., Chengdu 610000, PR China
通讯作者：
推荐引用方式(GB/T 7714)：
Tang Yu,Hu Yingjiang,Liu Weihao,et al.A radiopharmaceutical [89Zr]Zr-DFO-nimotuzumab for immunoPET with epidermal growth factor receptor expression in vivo.[J].Nuclear medicine and biology.2019,70:23-31.doi:10.1016/j.nucmedbio.2019.01.007.
APA：
Tang Yu,Hu Yingjiang,Liu Weihao,Chen Lin,Zhao Yan...&Liu Ning.(2019).A radiopharmaceutical [89Zr]Zr-DFO-nimotuzumab for immunoPET with epidermal growth factor receptor expression in vivo..Nuclear medicine and biology,70,
MLA：
Tang Yu,et al."A radiopharmaceutical [89Zr]Zr-DFO-nimotuzumab for immunoPET with epidermal growth factor receptor expression in vivo.".Nuclear medicine and biology 70.(2019):23-31

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