Boston Children's Hospital, Boston, MA, USA.
Nanomedicine (Lond). 2010 Oct;5(8):1183-91. doi: 10.2217/nnm.10.70.
Imaging of the lymphatic system is critical in preoperative planning of resections of complex lymphatic malformations. However, safe, effective imaging methods with sufficient resolution to identify the lymphatics have been lacking. In this study, we demonstrate the use of gadolinium-labeled dendrimers to image the lymphatics in small and large animal models during magnetic resonance lymphangiography.
Polyamidoamine G6-Gd_1B4M_N-hydroxysuccinimide was synthesized and administered intradermally in the extremities of normal mice and pigs at several doses.
The lymphatics were well demonstrated in both animal models and there was rapid uptake in the deep lymphatic system, including the thoracic duct. A significant dose reduction was achieved (1 µmol Gd/kg) in the 35-kg pig compared with mice, while still producing excellent results. No toxicity was observed and only minor inflammatory changes were observed at the injection site 30 days later.
We demonstrate that a low dose of a macromolecular magnetic resonance contrast agent can provide rapid imaging of the deep lymphatic system in both small and large animals. This data provides a basis to consider a similar agent in clinical trials.
在复杂淋巴管畸形切除术的术前规划中，淋巴系统的成像至关重要。然而，一直缺乏安全、有效的成像方法，其分辨率足以识别淋巴管。在这项研究中，我们展示了使用钆标记的树枝状大分子在磁共振淋巴造影术中对小动物和大动物模型中的淋巴管进行成像的方法。
合成聚酰胺胺 G6-Gd_1B4M_N-羟基琥珀酰亚胺，并在正常小鼠和猪的四肢以不同剂量皮内给药。
两种动物模型中均能很好地显示淋巴管，深淋巴管系统（包括胸导管）有快速摄取。与小鼠相比，在 35 公斤重的猪中实现了显著的剂量降低（1µmol Gd/kg），同时仍能产生出色的结果。未观察到毒性，仅在 30 天后注射部位观察到轻微的炎症变化。
我们证明了低剂量的大分子磁共振对比剂可快速对小动物和大动物的深部淋巴系统进行成像。该数据为考虑在临床试验中使用类似药物提供了依据。
