双靶向分子超声造影剂在前哨淋巴结中的特征描述。

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

机构信息

Department of Radiology, Thomas Jefferson University, 132 South 10th Street, Philadelphia, PA, 19107, USA.

Department of Pathology, Thomas Jefferson University, Philadelphia, PA, 19107, USA.

出版信息

Mol Imaging Biol. 2018 Apr;20(2):221-229. doi: 10.1007/s11307-017-1109-3.

DOI:10.1007/s11307-017-1109-3

PMID:28762204

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6535621/

Abstract

PURPOSE

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.

PROCEDURE

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 αβ-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.

RESULTS

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).

CONCLUSIONS

The results indicate that dual-targeted microbubbles labeled with P-selectin and αβ-integrin antibodies may aid in detecting metastatic involvement in SLNs of melanoma.

摘要

目的

本研究旨在评估双靶超声微泡在检测猪自然发生黑色素瘤模型中前哨淋巴结（SLN）转移疾病中的性能。SLN 是引流原发性肿瘤的淋巴链中的第一个淋巴结，早期检测转移性 SLN 受累对黑色素瘤的适当治疗至关重要。

方法

检查了 9 只携带自然发生黑色素瘤的 Sinclair 猪（体重 3-7 公斤；Sinclair BioResources，哥伦比亚，密苏里州，美国）。使用西门子 S3000 扫描仪和 9L4 探头进行成像（西门子医疗，山景城，加利福尼亚州）。使用靶向星 SA 微泡（Targeson，圣地亚哥，加利福尼亚州，美国）创建双靶对比剂，该微泡标记有 αβ-整合素和 P-选择素抗体。使用 IgG 标记的靶向星 SA 微泡作为对照。首先，在肿瘤周围注射 SonoVue 造影剂（GE Healthcare，奥斯陆，挪威）以检测 SLN。之后，在两次注射之间间隔 30 分钟，静脉注射双靶和 IgG 对照靶向星 SA 微泡。允许标记的靶向星 SA 微泡循环 4 分钟以实现结合。之后，在高强度破坏序列之前和之后采集几秒钟的两组图像剪辑。在放置于 SLN 上的感兴趣区域内，计算微泡破坏前后的平均强度差，作为靶向微泡对比剂保留的相对测量值。作为对照，对非 SLN 重复此过程。对所有影像学评估的淋巴结均进行手术切除，并进行组织学检查以确定是否存在转移性受累。

结果

共分析了 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受累大于 5%。所有非 SLN 均为良性。转移性 SLN 的双靶微泡的平均强度（±SD）明显高于良性淋巴结（18.05±19.11 与 3.30±6.65 AU；p=0.0008），而 IgG 标记的对照微泡在转移性和良性淋巴结之间显示出无差异保留的对比强度（0.39±1.14 与 0.03±0.24 AU；p=0.14）。