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Dynamic 18F-FDG PET Lymphography for In Vivo Identification of Lymph Node Metastases in Murine Melanoma
The Journal of Nuclear Medicine ( IF 9.3 ) Pub Date : 2018-02-01 , DOI: 10.2967/jnumed.117.196303
Hannah Lockau , Volker Neuschmelting , Anuja Ogirala , Antoni Vilaseca , Jan Grimm

Positron lymphography using 18F-FDG followed by Cerenkov-guided resection of lymph nodes in healthy mice has previously been introduced by our group. Our aim in this study was to further assess the technique’s potential beyond merely localizing sentinel lymph nodes. We now aimed to evaluate the potential of positron lymphography to characterize the nodes with respect to their tumor status in order to identify metastatic lymph nodes. We explored whether metastatic nodes could be distinguished from normal nodes via dynamic 18F-FDG lymphography, to then be resected under Cerenkov imaging guidance. Methods: A murine melanoma cell line highly metastatic to lymph nodes (B16F10) was implanted subcutaneously on the dorsal hind paw of C57 mice while the tumor-free contralateral leg served as an intraindividual control. A model of reactive lymph nodes after concanavalin A challenge served as an additional control to provide nonmalignant inflammatory lymphadenopathy. Dynamic PET/CT imaging was performed immediately after injection of 18F-FDG around the tumor or intracutaneously in the contralateral footpad. Furthermore, PET/CT and Cerenkov studies were performed repeatedly over time to follow the course of metastatic spread. In selected mice, popliteal lymph nodes underwent Cerenkov luminescence imaging. Hematoxylin and eosin staining was done to verify the presence of lymphatic melanoma infiltration. Results: Positron lymphography using 18F-FDG was successfully performed on tumor-bearing and non–tumor-bearing mice, as well as on controls bearing sites of inflammation; the results clearly identified the sentinel lymph node basin and delineated the lymphatic drainage. Significantly prolonged retention of activity was evident in metastatic nodes as compared with controls without tumor. On the basis of these results, the contrast in detection and identification of metastatic lymph nodes was distinct and could be used for guided lymph node resection, such as by using Cerenkov luminescence imaging. However, retention after 18F-FDG lymphography was also seen in acute inflammatory lymphadenopathy. Conclusion: In a tumor model, significantly longer retention of the radiotracer during 18F-FDG lymphography was seen in metastatic than nonmetastatic lymph nodes, allowing for differentiation between the two and for selective resection of tumor-bearing nodes using Cerenkov imaging. Inflammation can be better differentiated in a subacute state.



中文翻译:

动态18 F-FDG PET淋巴造影术用于体内鉴定小鼠黑色素瘤的淋巴结转移。

我们小组先前已经介绍了使用18 F-FDG进行正电子淋巴造影,然后在健康小鼠中进行切伦科夫引导的淋巴结切除术。我们在这项研究中的目的是进一步评估该技术的潜力,而不仅仅是定位前哨淋巴结。现在,我们旨在评估正电子淋巴照相术对淋巴结的肿瘤状态进行表征的潜力,以鉴定转移性淋巴结。我们探讨了是否可以通过动态18 F-FDG淋巴管造影将转移性淋巴结与正常淋巴结区分开,然后在切伦科夫成像指导下将其切除。方法:将高度转移至淋巴结的鼠黑色素瘤细胞系(B16F10)皮下植入C57小鼠的后爪,同时将无肿瘤的对侧腿作为单独的对照。伴刀豆球蛋白A攻击后的反应性淋巴结模型可作为提供非恶性炎性淋巴结病的附加对照。在肿瘤周围或对侧脚垫内皮内注射18 F-FDG后,立即进行动态PET / CT成像。此外,随着时间的推移,反复进行PET / CT和Cerenkov研究以追踪转移的过程。在选定的小鼠中,pop淋巴结接受Cerenkov发光成像。进行苏木精和曙红染色以验证淋巴黑色素瘤浸润的存在。结果:在荷瘤和非荷瘤小鼠以及带有炎症部位的对照组中,成功地使用18 F-FDG进行了正电子淋巴成像。结果清楚地确定了前哨淋巴结盆并描绘了淋巴引流。与没有肿瘤的对照相比,转移性淋巴结中明显延长了活性。根据这些结果,在转移性淋巴结的检测和鉴定中的对比是明显的,可以用于指导淋巴结切除,例如通过切伦科夫发光成像。然而,在急性炎症性淋巴结病中也观察到18 F-FDG淋巴造影后的retention留。结论:在肿瘤模型中,与非转移性淋巴结相比,转移性18 F-FDG淋巴结中放射性示踪剂的保留时间明显更长,从而可以区分两者,并可以通过切伦科夫成像术选择性切除带有肿瘤的淋巴结。在亚急性状态下,炎症可以得到更好的区分。

更新日期:2018-02-01
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