Optimization of Indocyanine Green for Intraoperative Fluorescent Image-Guided Localization of Lung Cancer; Analysis Based on Solid Component of Lung Nodule

SIMPLE SUMMARY: Multiple studies have performed intravenous injections of indocyanine green (ICG) for lung cancer detection, including primary and metastatic lung cancers. However, there is no consensus regarding the optimization of the ICG injection method. We optimized the ICG injection method (2 mg/kg at 12 h before surgery) using a rabbit model of lung cancer for the first time. Additionally, ICG-based cancer identifications are limited to solid tumors, and no study has examined lung ground-glass nodules (GGNs). We investigated the feasibility of ICG-based lung cancer imaging in adenocarcinoma presenting with GGNs and a consolidation-to-tumor (C/T) ratio ≤ 50% for the first time. Overall, 51 cases of lung cancer with a C/T ratio > 50% were successfully revealed with a 95% detection rate. Therefore, this study may provide guidance regarding ICG use for lung cancer detection, especially early-stage lung cancer. ABSTRACT: 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.