Detection of Mediastinal Lymph Node Metastases Using Indocyanine Green (ICG) Fluorescence Imaging in an Orthotopic Implantation Model

Background: The method of quickly identifying metastatic mediastinal lymph nodes has become an urgent problem for lung cancer surgery. Indocyanine green (ICG) has the characteristic of being retained in or around the lymph nodes; its pharmacokinetic characteristics and optimal imaging time have not yet been elucidated. Materials and Methods: The IVIS Lumina Imaging System was used to detect near infrared (NIR) fluorescence signals at different ICG doses, times and excitation/emission wavelengths in vitro. An artificial lymphogenous metastatic model of squamous lung carcinoma was established in 32 SCID-CB17 mice using Ma44.3 cells. An intratracheal injection of 1.25 ml/kg ICG (1.25x10(-2) mg/ml) was performed, then 780 nm Ex and 845 nm Em were used to visualize ICG at four different times. The metastatic mediastinal lymph nodes and the implanted local tumor site in the left lung were confirmed with bioluminescence and hematoxylin and eosin (H&E) staining of pathological specimens. Results: ICG had the strongest NIR fluorescence signal when using 780 nm Ex and 845 nm Em at 2 to 4 h after administrating 1.25x10(-2) mg/ml ICG in vitro. Combined with pathological H&E examination, fluorescence imaging of ICG reflected true-positive mediastinal metastasis of the mediastinum at 0.5 h and 2 h after the injection of ICG in vivo. While true-positive local tumor growth at the site of implantation in the left lung was reflected within 4 h after the injection of ICG. Conclusion: ICG was able to display the metastatic mediastinal lymph nodes within 2 h after endotracheal injection in an orthotopic squamous lung carcinoma implantation model.