乳腺癌前哨淋巴结活检术新型示踪剂的动物模型研究

The study of a novel tracer for breast cancer sentinel lymph node biopsy in an animal model

背景与目的:前哨淋巴结活检已成为临床腋淋巴结阴性早期乳腺癌患者的标准处理模式,并对疾病的分期和治疗方案的选择至关重要。该研究将吲哚菁绿和利妥昔单抗进行偶联作为新型示踪剂,采用小鼠后肢引流作为动物模型,模拟乳腺癌前哨淋巴结活检术,探索其定位效应。方法:小鼠后肢脚背皮下注射不同剂量的示踪剂,应用荧光脉管系统成像仪连续观测腘窝淋巴结(作为前哨淋巴结)至3 h,探索最佳注射剂量和显像时间。注射最佳剂量的示踪剂,观察至24 h,探索其持续定位效应。结果:随着注射剂量的增加,前哨淋巴结开始显像与达到最佳显像的时间均逐渐缩短,次级及第3级淋巴结显像率逐渐升高。新型示踪剂的最佳注射剂量为0.12μg(吲哚菁绿的含量),达最佳显像时间约为34 min。观察至24 h,前哨淋巴结显像率维持在100%,次级及第3级淋巴结显像率由6 h的0%和0%上升至20%和10%。结论:吲哚菁绿-利妥昔单抗能清晰定位前哨淋巴结且6 h内无次级淋巴结显像,具有较高的临床应用价值。

Background and purpose： Sentinel lymph node biopsy has replaced axillary lymph node dissec- tion as the standard staging procedure in early breast cancer patients with clinically negative axillary lymph nodes. It is a critical step for staging and treatment. This study investigated the localization effect of a novel tracer for breast cancer sentinel lymph node biopsy [indocyanine green （ICG）-rituximab （R）], using the hind limb drainage in mice as an animal model. Methods： For exploring the optimal dose and imaging time, different doses of ICG-R were injected subcutane- ously to the dorsurn of the foot in the BALB/c mice. Then the fluorescence vasculature imaging instrument was used continuously to observe the popliteal fossa lymph node （as sentinel lymph node） from the injection to 3 h after injection. For exploring the sustained localization effect, the optimal dose of ICG-R was injected and the imaging instrument was used from imaging to 24 h after injection. Results： The time from injection to imaging and the time from injection to the optimal imaging were shortened with the increased doses, and the imaging rate of the second or third level node increased accordingly. The best dosage of the novel tracer was 0.12 ~tg （dosage of indocyanine green） and the time from injection to the optimal imaging was about 34 rain. After the observation for 24 h, the imaging rate of sentinel lymph node was maintained at 100%, and the imaging rate of the second and the third level lymph node increased from 0% to 20% and 10%, respectively. Conclusion： ICG-R could clearly locate the sentinel lymph node. There is no imaging of the second level lymph node within 6 h. The novel tracer has high value in the clinical application.