Indocyanine green (ICG) has been used to detect several types of tumors; however, its ability to detect metastatic lymph nodes (LNs) remains unclear. Our goal was to determine the feasibility of ICG in detecting metastatic LNs. We established a mouse model and evaluated the potential of ICG. The feasibility of detecting metastatic LNs was also evaluated in patients with lung or esophageal cancer, detected with computed tomography (CT) or positron-emission tomography (PET)/CT, and scheduled to undergo surgical resection. Tumors and metastatic LNs were successfully detected in the mice. In the clinical study, the efficacy of ICG was evaluated in 15 tumors and fifty-four LNs with suspected metastasis or anatomically key regional LNs. All 15 tumors were successfully detected. Among the fifty-four LNs, eleven were pathologically confirmed to have metastasis; all eleven were detected in ICG fluorescence imaging, with five in CT and seven in PET/CT. Furthermore, thirty-four LNs with no signals were pathologically confirmed as nonmetastatic. Intravenous injection of ICG may be a useful tool to detect metastatic LNs and tumors. However, ICG is not a targeting agent, and its relatively low fluorescence makes it difficult to use to detect tumors in vivo. Therefore, further studies are needed to develop contrast agents and devices that produce increased fluorescence signals.

ICG fluorescence imaging has been used to detect lung cancer; however, there is no consensus regarding the optimization of the indocyanine green (ICG) injection method. The aim of this study was to determine the optimal dose and timing of ICG for lung cancer detection using animal models and to evaluate the feasibility of ICG fluorescence in lung cancer patients. In a preclinical study, twenty C57BL/6 mice with footpad cancer and thirty-three rabbits with VX2 lung cancer were used. These animals received an intravenous injection of ICG at 0.5, 1, 2, or 5 mg/kg, and the cancers were detected using a fluorescent imaging system after 3, 6, 12, and 24 h. In a clinical study, fifty-one patients diagnosed with lung cancer and scheduled to undergo surgery were included. Fluorescent images of lung cancer were obtained, and the fluorescent signal was quantified. Based on a preclinical study, the optimal injection method for lung cancer detection was 2 mg/kg ICG 12 h before surgery. Among the 51 patients, ICG successfully detected 37 of 39 cases with a consolidation-to-tumor (C/T) ratio of >50% (TNR: 3.3 ± 1.2), while it failed in 12 cases with a C/T ratio ≤ 50% and 2 cases with anthracosis. ICG injection at 2 mg/kg, 12 h before surgery was optimal for lung cancer detection. Lung cancers with the C/T ratio > 50% were successfully detected using ICG with a detection rate of 95%, but not with the C/T ratio ≤ 50%. Therefore, further research is needed to develop fluorescent agents targeting lung cancer.

Treatments for lung adenocarcinoma, a type of non-small-cell lung cancer that accounts for about 40% of all lung cancers, are generally administered intravenously, thus causing systemic side effects and poor pulmonary delivery. Inhalation therapy has been investigated to overcome these limitations; however, it shows limited delivery of drugs to the distal lung region, rapid clearance by alveolar macrophages, and immune responses due to synthetic materials. In this study, we developed inhalable nanotherapeutics to treat lung adenocarcinoma using exogenous pulmonary surfactant (PS) that are lipid-based, clinically used, and easy to fuse with the endogenous PS layer in the alveolar space. We prepared PS-based nanovesicles (PSNVs) using the thin-film hydration method followed by extrusion. PSNVs interacted selectively with alveolar type II cell-derived adenocarcinoma cells in vitro and retained long in the alveolar space of mice after inhalation, presumably due to the incorporated PS proteins. Furthermore, inhalation treatments of paclitaxel-loaded PSNVs significantly inhibited the tumor growth in the lungs of the orthotopic lung cancer mouse model established by intratracheally injection of A549 cells into nude mice, compared with free paclitaxel and paclitaxel-loaded synthetic NVs. These results suggest that the use of PSNVs for inhalation delivery of a wide range of therapeutic agents has great potential for the treatment of various lung diseases, including lung adenocarcinoma.