首页> 外文会议>Energy-based treatment of tissue and assessment IX >A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation
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A ferritin-containing nanoconjugate as MRI image-guidance to target Necl-5, a tumor-surface antigen: a potential thermal accelerant for microwave ablation

机译:含铁蛋白的纳米共轭物作为MRI图像的靶标,靶向肿瘤表面抗原Necl-5:微波消融的潜在热促进剂

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摘要

ABSTRACTS Purpose: A ferritin-containing nanoparticle conjugated with a target-specific antibody was investigated as a MRI contrast agent for tumor detection. A genetically modified ferritin to markedly improve Fe (III) payload (up to 7,000 Fe ions), was chemically tethered to a monoclonal antibody against rat Nectin-like molecule 5 (Necl-5). Necl-5 is a cell surface glycoprotein that is highly expressed on the cell surface of many common epithelial cancers, including prostate cancer. It was previously demonstrated that this novel nanoconjugate agent exhibited effective in vitro targeting of Necl- 5 expressing tumor cells and exhibited strong MRI contrast characteristics via shortening of T2. Here, we demonstrate that the nanoconjugate-Necl-5 interaction can be exploited to target and detect tumor in vivo by MRI. Procedure: Using an in vivo tumor model (i.e., tumor size 0.5-1 cm, immunodeficient beigeude/xid mouse, xenograft injection with transformed rat prostate cells), efficacy of the conjugate targeting the tumor was examined. We used two injection strategies, a direct and a tail vein injection (0.8 mg, 300 μL per subject). Pre-injection baseline and post- injection scans were performed with the following spin-echo sequence parameters: Field of view = 90x53mm, reconstruction matrix size = 192x114, slice thickness = 1mm (10 slices), repetition time (TR) = 2070 ms, echo times (TE) = 11-198 ms in 1 lms steps (18 echoes), number of averages = 2, acquisition time per scan = 7min 56s. Results: All T2 data obtained were converted to R2 for demonstration purposes (R2 = 1/T2). The tail vein injected conjugate significantly increased R2 response (22.9 ± 5.2 s~(-1)) as compared to control (13.5 ± 1.7 s~(-1)) at 4 h. The weaker R2 increase was noted (15.2 ± 2.0 s~(-1)) at 24 h. No notable changes in R2 were observed in surrounding tissues regardless the stages of the measurement. We also measured the initial conjugate kinetics for both injection methods with respect to the ability of targeting the tumor. Direct injection of the nanoconjugate in to the center of the tumor showed a stronger and more rapid increase in R2 than the tail vein injection. Conclusion: The nanoconjugate interacts strongly and selectively in situ with Necl-5 overexpressing tumor cells. Direct injection of the nanoconjugate into the body of the tumor caused a more significant in situ R2 increase in MRI than the tail vein injection. Varying degrees of R2 increase within the tumor mass is likely to represent different distribution patterns of the conjugate, reflective of tumor heterogeneity.
机译:摘要:目的:研究了与目标特异性抗体偶联的含铁蛋白的纳米颗粒,作为用于肿瘤检测的MRI造影剂。基因修饰的铁蛋白可显着改善Fe(III)的有效载荷(最多7,000 Fe离子),通过化学方式与抗鼠Nectin样分子5(Necl-5)的单克隆抗体结合。 Necl-5是一种细胞表面糖蛋白,在许多常见的上皮癌(包括前列腺癌)的细胞表面上高度表达。先前已证明,这种新型纳米偶联剂对Nec-5表达肿瘤细胞具有有效的体外靶向作用,并通过缩短T2表现出很强的MRI对比特征。在这里,我们证明了纳米共轭物-Necl-5相互作用可以被用来通过MRI靶向和检测体内肿瘤。程序:使用体内肿瘤模型(即,肿瘤大小0.5-1cm,免疫缺陷的米色/裸鼠/ xid小鼠,异种移植注射转化的大鼠前列腺细胞),检查了靶向肿瘤的缀合物的功效。我们使用了两种注射策略,直接和尾静脉注射(0.8 mg,每个受试者300μL)。使用以下自旋回波序列参数执行进样前基线和进样后扫描:视野= 90x53mm,重建矩阵尺寸= 192x114,切片厚度= 1mm(10切片),重复时间(TR)= 2070 ms,回波时间(TE)= 11-198毫秒,步长为1 lms(18个回波),平均数= 2,每次扫描的采集时间= 7分钟56s。结果:出于演示目的,将所有获得的T2数据转换为R2(R2 = 1 / T2)。与对照组相比,在4 h时,尾静脉注射的结合物显着提高了R2反应(22.9±5.2 s〜(-1))。在24 h时R2的增加较弱(15.2±2.0 s〜(-1))。无论测量的阶段如何,在周围组织中均未观察到R2的显着变化。我们还针对靶向肿瘤的能力测量了两种注射方法的初始共轭动力学。与尾静脉注射相比,将纳米缀合物直接注射到肿瘤中心显示R2的增加更强,更快。结论:纳米共轭物与过量表达Necl-5的肿瘤细胞发生强烈而选择性的原位相互作用。将纳米共轭物直接注射到肿瘤体内会比尾静脉注射在MRI中引起更显着的原位R2增加。 R2在肿瘤块内的变化程度可能代表结合物的不同分布模式,反映了肿瘤的异质性。

著录项

  • 来源
    《Energy-based treatment of tissue and assessment IX》|2017年|100660H.1-100660H.9|共9页
  • 会议地点 San Francisco(US)
  • 作者单位

    Department of Diagnostic Imaging, Division of Molecular Imaging, Rhode Island Hospital/ The Warren Alpert Medical School of Brown University, Providence, RI, USA;

    Department of Medicine, Division of Hematology and Oncology, Rhode Island Hospital/ The Warren Alpert Medical School of Brown University, Providence, RI, USA;

    Division of Bioengineering, Nanyang Technological University, Singapore;

    Division of Bioengineering, Nanyang Technological University, Singapore;

    Department of Diagnostic Imaging, Division of Molecular Imaging, Rhode Island Hospital/ The Warren Alpert Medical School of Brown University, Providence, RI, USA;

    Department of Diagnostic Imaging, Division of Molecular Imaging, Rhode Island Hospital/ The Warren Alpert Medical School of Brown University, Providence, RI, USA;

    Department of Diagnostic Imaging, Division of Molecular Imaging, Rhode Island Hospital/ The Warren Alpert Medical School of Brown University, Providence, RI, USA;

    Department of Diagnostic Imaging, Division of Molecular Imaging, Rhode Island Hospital/ The Warren Alpert Medical School of Brown University, Providence, RI, USA;

    Department of Diagnostic Imaging, Division of Molecular Imaging, Rhode Island Hospital/ The Warren Alpert Medical School of Brown University, Providence, RI, USA;

    Brown University Institute for Brain Science, Providence, RI, USA,Brown University Department of Neuroscience, Providence, RI, USA;

    Department of Diagnostic Imaging, Division of Molecular Imaging, Rhode Island Hospital/ The Warren Alpert Medical School of Brown University, Providence, RI, USA;

  • 会议组织
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Ferritin; nanoconjugate; Necl-5; monoclonal antibody; Xenograft; T_1 and T_2 (R_1 and R_2); electromagnetic field; self-assembly; microwave energy;

    机译:铁蛋白;纳米共轭物; Necl-5;单克隆抗体;异种移植; T_1和T_2(R_1和R_2);电磁场自组装;微波能量;

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