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Novel "Add-On" Molecule Based on Evans Blue Confers Superior Pharmacokinetics and Transforms Drugs to Theranostic Agents
被引:67
作者:

Chen, Haojun
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机构:
Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Hosp, Dept Nucl Med, Xiamen, Peoples R China
NIH, Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, 35A Convent Dr,GD937, Bethesda, MD 20892 USA Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Hosp, Dept Nucl Med, Xiamen, Peoples R China

Jacobson, Orit
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NIH, Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, 35A Convent Dr,GD937, Bethesda, MD 20892 USA Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Hosp, Dept Nucl Med, Xiamen, Peoples R China

Niu, Gang
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h-index: 0
机构:
NIH, Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, 35A Convent Dr,GD937, Bethesda, MD 20892 USA Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Hosp, Dept Nucl Med, Xiamen, Peoples R China

Weiss, Ido D.
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机构:
NIH, Natl Inst Allergy & Infect Dis, Lab Mol Immunol, Bethesda, MD USA Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Hosp, Dept Nucl Med, Xiamen, Peoples R China

Kiesewetter, Dale.
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NIH, Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, 35A Convent Dr,GD937, Bethesda, MD 20892 USA Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Hosp, Dept Nucl Med, Xiamen, Peoples R China

Liu, Yi
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NIH, Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, 35A Convent Dr,GD937, Bethesda, MD 20892 USA Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Hosp, Dept Nucl Med, Xiamen, Peoples R China

Ma, Ying
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NIH, Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, 35A Convent Dr,GD937, Bethesda, MD 20892 USA Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Hosp, Dept Nucl Med, Xiamen, Peoples R China

Wu, Hua
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h-index: 0
机构:
Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Hosp, Dept Nucl Med, Xiamen, Peoples R China Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Hosp, Dept Nucl Med, Xiamen, Peoples R China

Chen, Xiaoyuan
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h-index: 0
机构:
NIH, Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, 35A Convent Dr,GD937, Bethesda, MD 20892 USA Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Hosp, Dept Nucl Med, Xiamen, Peoples R China
机构:
[1] Xiamen Univ, Affiliated Hosp 1, Xiamen Canc Hosp, Dept Nucl Med, Xiamen, Peoples R China
[2] NIH, Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, 35A Convent Dr,GD937, Bethesda, MD 20892 USA
[3] NIH, Natl Inst Allergy & Infect Dis, Lab Mol Immunol, Bethesda, MD USA
基金:
中国国家自然科学基金;
美国国家卫生研究院;
关键词:
Evans blue;
albumin binding;
RGD peptide;
integrin;
theranostics;
Y-90;
INTEGRIN ALPHA(V)BETA(3);
ALBUMIN-BINDING;
MOUSE MODEL;
THERAPY;
PEPTIDE;
PROTEINS;
ALPHA;
PET;
D O I:
10.2967/jnumed.116.182097
中图分类号:
R8 [特种医学];
R445 [影像诊断学];
学科分类号:
1002 ;
100207 ;
1009 ;
摘要:
One of the major design considerations for a drug is its pharmacokinetics in the blood. A drug with a short half-life in the blood is less available at a target organ. Such a limitation dictates treatment with either high doses or more frequent doses, both of which may increase the likelihood of undesirable side effects. To address the need for additional methods to improve the blood half-life of drugs and molecular imaging agents, we developed an "add-on" molecule that contains 3 groups: a truncated Evans blue dye molecule that binds to albumin with a low micromolar affinity and provides a prolonged half-life in the blood; a metal chelate that allows radiolabeling for imaging and radiotherapy; and maleimide for easy conjugation to drug molecules. Methods: The truncated Evans blue molecule was conjugated with the chelator NOTA or DOTA, and the resulting conjugate was denoted as NMEB or DMEB, respectively. As a proof of concept, we coupled NMEB and DMEB to c(RGDfK), which is a small cyclic arginine-glycine-aspartic acid (RGD) peptide, for targeting integrin alpha(v)beta(3). NMEB and DMEB were radiolabeled with Cu-64 and Y-90, respectively, and tested in xenograft models. Results: The resulting radiolabeled conjugates showed a prolonged circulation half-life and enhanced tumor accumulation in integrin alpha(v)beta(3)-expressing tumors. Tumor uptake was markedly improved over that with NOTA- or DOTA-conjugated c(RGDfK). Tumor radiotherapy experiments in mice with Y-90-DMEB-RGD showed promising results; existing tumors were eliminated. Conclusion: Conjugation of our novel add-on molecule, NMEB or DMEB, to potential tracers or therapeutic agents improved blood half-life and tumor uptake and could transform such agents into theranostic entities.
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收藏
页码:590 / 597
页数:8
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论文数: 0 引用数: 0
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机构: Univ Missouri, Sch Med, Dept Internal Med, Columbia, MO USA
[10]
Herpes Simplex Virus Glycoproteins H/L Bind to Cells Independently of αVβ3 Integrin and Inhibit Virus Entry, and Their Constitutive Expression Restricts Infection
[J].
Gianni, Tatiana
;
Cerretani, Arianna
;
DuBois, Rebecca
;
Salvioli, Stefano
;
Blystone, Scott S.
;
Rey, Felix
;
Campadelli-Fiume, Gabriella
.
JOURNAL OF VIROLOGY,
2010, 84 (08)
:4013-4025

Gianni, Tatiana
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机构:
Alma Mater Studiorum Univ Bologna, Dept Expt Pathol, Sect Microbiol & Virol, I-40126 Bologna, Italy Alma Mater Studiorum Univ Bologna, Dept Expt Pathol, Sect Microbiol & Virol, I-40126 Bologna, Italy

Cerretani, Arianna
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机构:
Alma Mater Studiorum Univ Bologna, Dept Expt Pathol, Sect Microbiol & Virol, I-40126 Bologna, Italy Alma Mater Studiorum Univ Bologna, Dept Expt Pathol, Sect Microbiol & Virol, I-40126 Bologna, Italy

DuBois, Rebecca
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机构:
Inst Pasteur, Unite Virol Struct, Paris, France
CNRS, Unite Rech Associee 3015, Paris, France Alma Mater Studiorum Univ Bologna, Dept Expt Pathol, Sect Microbiol & Virol, I-40126 Bologna, Italy

Salvioli, Stefano
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机构:
Alma Mater Studiorum Univ Bologna, Dept Expt Pathol, Sect Microbiol & Virol, I-40126 Bologna, Italy Alma Mater Studiorum Univ Bologna, Dept Expt Pathol, Sect Microbiol & Virol, I-40126 Bologna, Italy

Blystone, Scott S.
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机构:
SUNY Upstate Med Univ, Dept Cell & Dev Biol, Syracuse, NY USA Alma Mater Studiorum Univ Bologna, Dept Expt Pathol, Sect Microbiol & Virol, I-40126 Bologna, Italy

Rey, Felix
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h-index: 0
机构:
Inst Pasteur, Unite Virol Struct, Paris, France
CNRS, Unite Rech Associee 3015, Paris, France Alma Mater Studiorum Univ Bologna, Dept Expt Pathol, Sect Microbiol & Virol, I-40126 Bologna, Italy

Campadelli-Fiume, Gabriella
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机构:
Alma Mater Studiorum Univ Bologna, Dept Expt Pathol, Sect Microbiol & Virol, I-40126 Bologna, Italy Alma Mater Studiorum Univ Bologna, Dept Expt Pathol, Sect Microbiol & Virol, I-40126 Bologna, Italy