Sentinel Lymph Node Characterization with a Dual-Targeted Molecular Ultrasound Contrast Agent.

Sentinel Lymph Node Characterization with a Dual-Targeted Molecular Ultrasound Contrast Agent.
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DOI:
10.1007/s11307-017-1109-3
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发表时间:
2018-04
影响因子:
3.1
通讯作者:
Lyshchik A
Lyshchik A
中科院分区:
医学3区
文献类型:
--
作者:
Nam K;Stanczak M;Forsberg F;Liu JB;Eisenbrey JR;Solomides CC;Lyshchik A

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本研究的目的是评估双靶向微泡分子超声检测天然黑色素瘤猪模型前哨淋巴结 (SLN) 转移性疾病的性能。 SLN 是引流原发肿瘤的淋巴链中的第一个淋巴结,早期发现转移性 SLN 受累对于黑色素瘤的适当治疗至关重要。对九只患有天然黑色素瘤的辛克莱猪(体重 3-7 公斤;辛克莱生物资源公司,哥伦比亚,密苏里州,美国)进行了检查。使用带有 9L4 探头的西门子 S3000 扫描仪进行成像(Siemens Healthineers,山景城,加利福尼亚州)。使用标有 αvβ3-整合素和 P-选择素抗体的 Targestar SA 微泡(Targeson,圣地亚哥,加利福尼亚州,美国)创建双靶向造影剂。使用带有 IgG 标记的 Targestar SA 微泡作为对照。首先,瘤周注射 Sonazoid 造影剂(GE Healthcare,奥斯陆,挪威)来检测 SLN。之后,静脉注射双靶向和 IGG 对照 Targestar SA 微泡,注射间隔 30 分钟。让标记的 Targestar SA 微泡循环 4 分钟以实现结合。此后,在高功率破坏序列之前和之后几秒钟采集了两组图像片段。计算 SLN 上感兴趣区域内气泡破坏前后的平均强度差,作为目标微泡造影剂保留的相对测量值。对于作为对照的非 SLN 重复此过程。通过手术切除所有影像学评估的淋巴结,并进行组织学检查是否存在转移灶。分析中总共包括 43 个淋巴结(25 个 SLN 和 18 个非 SLN),其中 18 个 SLN 在组织学上显示转移灶大于 5%。所有非 SLN 均为良性。转移性 SLN 的双靶向微泡的平均强度 (± SD) 显着高于良性 LN(18.05 ± 19.11 与 3.30 ± 6.65 AU;p = 0.0008),而 IgG 标记的对照微泡显示转移性淋巴结和良性淋巴结之间的保留对比强度没有差异(0.39 ± 1.14 与 0.03) ±0.24AU;p=0.14)。结果表明,用 P-选择素和 αvβ3-整合素抗体标记的双靶向微泡可能有助于检测黑色素瘤 SLN 的转移情况。
The purpose of this study was to assess the performance of molecular ultrasound with dual-targeted microbubbles to detect metastatic disease in the sentinel lymph nodes (SLNs) in swine model of naturally occurring melanoma. The SLN is the first lymph node in the lymphatic chain draining primary tumor, and early detection of metastatic SLN involvement is critical in the appropriate management of melanoma. Nine Sinclair swine (weight 3–7 kg; Sinclair BioResources, Columbia, MO, USA) with naturally occurring melanoma were examined. Siemens S3000 scanner with a 9L4 probe was used for imaging (Siemens Healthineers, Mountain View, CA). Dual-targeted contrast agent was created using Targestar SA microbubbles (Targeson, San Diego, CA, USA) labeled with αvβ3-integrin and P-selectin antibodies. Targestar SA microbubbles labeled with IgG-labeled were used as control. First, peritumoral injection of Sonazoid contrast agent (GE Healthcare, Oslo, Norway) was performed to detect SLNs. After that, dual-targeted and IGG control Targestar SA microbubbles were injected intravenously with a 30-min interval between injections. Labeled Targestar SA microbubbles were allowed to circulate for 4 min to enable binding. After that, two sets of image clips were acquired several seconds before and after a high-power destruction sequence. The mean intensity difference pre- to post-bubble destruction within the region of interest placed over SLN was calculated as a relative measure of targeted microbubble contrast agent retention. This process was repeated for non-SLNs as controls. All lymph nodes evaluated on imaging were surgically removed and histologically examined for presence of metastatic involvement. A total of 43 lymph nodes (25 SLNs and 18 non-SLNs) were included in the analysis with 18 SLNs demonstrating metastatic involvement greater than 5 % on histology. All non-SLNs were benign. The mean intensity (± SD) of the dual-targeted microbubbles for metastatic SLNs was significantly higher than that of benign LNs (18.05 ± 19.11 vs. 3.30 ± 6.65 AU; p = 0.0008), while IgG-labeled control microbubbles demonstrated no difference in retained contrast intensity between metastatic and benign lymph nodes (0.39 ± 1.14 vs. 0.03 ± 0.24 AU; p = 0.14). The results indicate that dual-targeted microbubbles labeled with P-selectin and αvβ3-integrin antibodies may aid in detecting metastatic involvement in SLNs of melanoma.
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