Melancon Marites P, Wang Yuetang, Wen Xiaoxia, Bankson James A, Stephens L Clifton, Jasser Samar, Gelovani Juri G, Myers Jeffrey N, Li Chun
Departments of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Invest Radiol. 2007 Aug;42(8):569-78. doi: 10.1097/RLI.0b013e31804f5a79.
To evaluate the effectiveness of a dual magnetic resonance-near infrared fluorescence optical imaging agent, poly(l-glutamic acid)-DTPA-Gd-NIR813, for both preoperative and intraoperative visualization and characterization of sentinel lymph nodes (SLN) in mice.
Poly(L-glutamic acid) was conjugated with DTPA-Gd and NIR813 dye to obtain PG-DTPA-Gd-NIR813. To confirm drainage into the SLNs, this agent was injected subcutaneously into the front paw of nude mice followed by isosulfan blue (n = 6). Furthermore, PG-DTPA-Gd-NIR813 was injected subcutaneously at doses of 0.002 mmol Gd/kg (4.8 nmol eq. NIR813) and 0.02 mmol Gd/kg (48 nmol eq. NIR813) (n = 3/dose). To differentiate metastatic from nonmetastatic lymph nodes, nude mice bearing human oral squamous cell carcinoma (DM14) were injected intralingually with 0.02 mmol Gd/kg PG-DTPA-Gd-NIR813 (n = 3). Pre- and postcontrast images were taken using 4.7 T Bruker MRI scanner and Xenogen optical imaging system. The status of lymph nodes resected under the guidance of optical imaging was confirmed by histologic examinations.
PG-DTPA-Gd-NIR813 colocalized with isosulfan blue, indicating drainage to the SLN. After subcutaneous injection, axiliary and branchial lymph nodes were clearly visualized with both T1-weighted MR and optical imaging within 3 minutes of contrast injection, even at the lowest dose tested (0.002 mmol Gd/kg). After intralingual injection in tumor-bearing mice, MR imaging identified 4 of the 6 superficial cervical lymph nodes, whereas near-infrared fluorescence (NIRF) optical imaging identified all 6 cervical nodes. The pattern of contrast enhancement of SLN visualized in MR images showed a characteristic ring-shaped appearance with a central filling defect, possibly resulting from nodal infiltration of metastatic lesions. Histopathologic examination of the SLNs resected under NIRF imaging guidance revealed micrometastases in all 6 SLNs identified by NIRF imaging.
The dual modality imaging method demonstrated in this study represents an effective technique for localization and characterization of SLN.
评估双模态磁共振 - 近红外荧光光学成像剂聚（L - 谷氨酸）- DTPA - Gd - NIR813在小鼠前哨淋巴结（SLN）术前及术中可视化和特征描述方面的有效性。
将聚（L - 谷氨酸）与DTPA - Gd和NIR813染料偶联，得到PG - DTPA - Gd - NIR813。为确认其是否引流至前哨淋巴结，将该试剂皮下注射到裸鼠前爪，随后注射异硫蓝（n = 6）。此外，分别以0.002 mmol Gd/kg（4.8 nmol当量NIR813）和0.02 mmol Gd/kg（48 nmol当量NIR813）的剂量皮下注射PG - DTPA - Gd - NIR813（每个剂量n = 3）。为区分转移性和非转移性淋巴结，将携带人口腔鳞状细胞癌（DM14）的裸鼠舌内注射0.02 mmol Gd/kg的PG - DTPA - Gd - NIR813（n = 3）。使用4.7 T布鲁克MRI扫描仪和Xenogen光学成像系统采集对比前后的图像。通过组织学检查确认在光学成像引导下切除的淋巴结状态。
PG - DTPA - Gd - NIR813与异硫蓝共定位，表明其引流至前哨淋巴结。皮下注射后，即使在测试的最低剂量（0.002 mmol Gd/kg）下，注射对比剂后3分钟内，T1加权磁共振成像和光学成像均可清晰显示腋窝和支气管淋巴结。在荷瘤小鼠舌内注射后磁共振成像识别出6个颈浅淋巴结中的4个，而近红外荧光（NIRF）光学成像识别出所有6个颈淋巴结。磁共振图像中可视化的前哨淋巴结对比增强模式显示出特征性的环形外观，中央有充盈缺损，这可能是由于转移性病变的淋巴结浸润所致。在NIRF成像引导下切除的前哨淋巴结的组织病理学检查显示，NIRF成像识别出的所有6个前哨淋巴结均有微转移。
本研究中展示的双模态成像方法是一种用于前哨淋巴结定位和特征描述的有效技术。
