[1]Yingding Xu,Gang Ren,Shibo Qi,等.Profiling EGFR in Triple Negative Breast Tumor Using Affibody PET Imaging[J].国际放射医学核医学杂志,2016,40(5):329-337.[doi:10.3760/cma.j.issn.1673-4114.2016.05.002]
　Yingding Xu,Gang Ren,Shibo Qi,et al.Profiling EGFR in Triple Negative Breast Tumor Using Affibody PET Imaging[J].International Journal of Radiation Medicine and Nuclear Medicine,2016,40(5):329-337.[doi:10.3760/cma.j.issn.1673-4114.2016.05.002]
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Profiling EGFR in Triple Negative Breast Tumor Using Affibody PET Imaging(/HTML)
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
40
期数:
2016年第5期
页码:
329-337
栏目:
论著
出版日期:
2016-09-25

文章信息/Info

Title:
Profiling EGFR in Triple Negative Breast Tumor Using Affibody PET Imaging
作者:
Yingding Xu;  Gang Ren;  Shibo Qi;  Zhen Cheng
Molecular Imaging Program at Stanford(MIPS), Department of Radiology and Bio-X Program, Stanford University, California, 94305-5344
Author(s):
Yingding Xu;  Gang Ren;  Shibo Qi;  Zhen Cheng
Molecular Imaging Program at Stanford(MIPS), Department of Radiology and Bio-X Program, Stanford University, California, 94305-5344
关键词:
Affibody; Epidermal grown factor receptor; Positron-emission tomography; Triple negative breast heoplasms; Copper radioisotopes
Keywords:
Affibody; Epidermal grown factor receptor; Positron-emission tomography; Triple negative breast heoplasms; Copper radioisotopes
DOI:
10.3760/cma.j.issn.1673-4114.2016.05.002
摘要:
Objective Triple negative breast cancer(TNBC) represents a group of refractory breast cancers with aggressive clinical manifestations as well as poor prognoses. Human epidermal growth factor receptor(EGFR) expression is strongly associated with TNBC progression and it may serve as a therapeutic target for TNBC. We aimed to evaluate EGFR affibody-based PET imaging to profile EGFR expression in small animal models. Methods 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA) conjugated Ac-Cys-ZEGFR:1907 was chemically synthesized using solid phase peptide synthesizer and then radiolabeled with 64Cu. The in vitro cell uptake study was performed using SUM159 and MCF7 cells. The biodistribution and small animal PET imaging using 64Cu-DOTA-ZEGFR:1907 were further carried out with nude mice bearing subcutaneous MDA-MB-231 and SUM159 tumors. Results DOTA-Ac-Cys-ZEGFR:1907 was successfully synthesized and radiolabeled with 64Cu. Biodistribution study showed that tumor uptake value of 64Cu-DOTA-Ac-Cys-ZEGFR:1907 remained at(4.07±0.93)%ID/g at 24 h in nude mice(n=4) bearing SUM159 xenografts. Furthermore, small animal PET imaging study clearly showed that 64Cu-DOTA-Ac-Cys-ZEGFR:1907 specifically delineated the EGFR positive TNBC tumors at 4 h or later. Conclusion The study demonstrates that 64Cu-DOTA-Ac-Cys-ZEGFR:1907 is a promising molecular probe for PET imaging of EGFR positive TNBC. EGFR based small protein scaffold holds great promise as a novel platform that can be used for EGFR profiling of TNBC.
Abstract:
Objective Triple negative breast cancer(TNBC) represents a group of refractory breast cancers with aggressive clinical manifestations as well as poor prognoses. Human epidermal growth factor receptor(EGFR) expression is strongly associated with TNBC progression and it may serve as a therapeutic target for TNBC. We aimed to evaluate EGFR affibody-based PET imaging to profile EGFR expression in small animal models. Methods 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA) conjugated Ac-Cys-ZEGFR:1907 was chemically synthesized using solid phase peptide synthesizer and then radiolabeled with 64Cu. The in vitro cell uptake study was performed using SUM159 and MCF7 cells. The biodistribution and small animal PET imaging using 64Cu-DOTA-ZEGFR:1907 were further carried out with nude mice bearing subcutaneous MDA-MB-231 and SUM159 tumors. Results DOTA-Ac-Cys-ZEGFR:1907 was successfully synthesized and radiolabeled with 64Cu. Biodistribution study showed that tumor uptake value of 64Cu-DOTA-Ac-Cys-ZEGFR:1907 remained at(4.07±0.93)%ID/g at 24 h in nude mice(n=4) bearing SUM159 xenografts. Furthermore, small animal PET imaging study clearly showed that 64Cu-DOTA-Ac-Cys-ZEGFR:1907 specifically delineated the EGFR positive TNBC tumors at 4 h or later. Conclusion The study demonstrates that 64Cu-DOTA-Ac-Cys-ZEGFR:1907 is a promising molecular probe for PET imaging of EGFR positive TNBC. EGFR based small protein scaffold holds great promise as a novel platform that can be used for EGFR profiling of TNBC.

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备注/Memo

备注/Memo:
收稿日期:2016-07-18
基金项目:Office of Science(BER), U.S. Department of Energy(DE-SC0008397); California Breast Cancer Research Program(14IB-0091); National Cancer Institute Small Animal Imaging Resource Program Grant (R24 CA93862); In Vivo Cellular Molecular Imaging Center Grant (P50 CA114747, 5R01CA119053)
通讯作者:Cheng Z, Email:zcheng@stanford.edu
更新日期/Last Update: 1900-01-01