SIMPLIFIED PREPARATION OF αvβ3 INTEGRIN-TARGETED MICROBUBBLES BASED ON A CLINICALLY AVAILABLE ULTRASOUND CONTRAST AGENT: VALIDATION IN A TUMOR-BEARING MOUSE MODEL

被引:11
作者
Otani, Kentaro [1 ]
Nishimura, Hirohito [2 ]
Kamiya, Atsunori [3 ]
Harada-Shiba, Mariko [1 ,4 ]
机构
[1] Natl Cerebral & Cardiovasc Ctr, Dept Regenerat Med & Tissue Engn, Res Inst, Osaka, Japan
[2] Natl Cerebral & Cardiovasc Ctr, Dept Biochem, Res Inst, Osaka, Japan
[3] Natl Cerebral & Cardiovasc Ctr, Dept Cardiovasc Dynam, Res Inst, Osaka, Japan
[4] Natl Cerebral & Cardiovasc Ctr, Dept Mol Innovat Lipidol, Res Inst, Osaka, Japan
关键词
Microbubbles; Ultrasound molecular imaging; Sonazoid; Lactadherin; Tumor angiogenesis; IN-VIVO; ANGIOGENESIS; BR55; IDENTIFICATION; FEASIBILITY; THERAPY; BINDING; CANCER; VITRO;
D O I
10.1016/j.ultrasmedbio.2018.01.017
中图分类号
O42 [声学];
学科分类号
070206 ; 082403 ;
摘要
The usefulness of ultrasound molecular imaging with alpha(v)beta(3) integrin-targeted microbubbles for detecting tumor angiogenesis has been demonstrated. Recently, we developed alpha(v)beta(3) integrin-targeted microbubbles by modifying clinically available microbubbles (Sonazoid, Daiichi-Sankyo Pharmaceuticals, Tokyo, Japan) with a secreted glycoprotein (lactadherin). The aims of our present study were to simplify the preparation of lactadherin-bearing Sonazoid and to examine the diagnostic utility of lactadherin-bearing Sonazoid for alpha(v)beta(3) integrin-expressing tumor vessels by using SK-OV-3-tumor-bearing mice. By incubating 1.2 x 107 Sonazoid microbubbles with 1.0 mu g lactadherin, the complicated washing and centrifugation steps during the microbubble preparation could be omitted with no significant reduction in labeling ratio of lactadherin-bearing Sonazoid. In addition, the number of Sonazoid microbubbles accumulated in the SK-OV-3 tumor was significantly increased by modifying Sonazoid with lactadherin. Our data suggest that the lactadherin-bearing Sonazoid is an easily prepared and potentially clinically translatable targeted microbubble for alpha(v)beta(3) integrin-expressing vessels. (E-mail: otani@ncvc.go.jp) (c) 2018 World Federation for Ultrasound in Medicine & Biology. All rights reserved.
引用
收藏
页码:1063 / 1073
页数:11
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