Optimization of Second Window Indocyanine Green for Intraoperative Near-Infrared Imaging of Thoracic Malignancy

Abstract

Background: Near-infrared (NIR) imaging using the second time window of indocyanine green (ICG) allows localization of pulmonary, pleural, and mediastinal malignancies during surgery. Based on empirical evidence, we hypothesized that different histological tumor types fluoresce optimally at different ICG doses. Study Design: Patients with thoracic tumors biopsy-proven or suspicious for malignancy were enrolled in an NIR imaging clinical trial. Patients received a range of ICG doses one day prior to surgery: 1 mg/kg (n=8), 2 mg/kg (n=8), 3 mg/kg (n=13), 4 mg/kg (n=8), and 5 mg/kg (n=8). Intraoperatively, NIR imaging was performed. The endpoint was to identify the highest tumortobackground fluorescence ratio (TBR) for each tumor type at each dose. Final pathology confirmed tumor histology. Results: Of 45 patients, 41 had malignancies (18 non-small cell lung cancer (NSCLC), 3 pulmonary neuroendocrine tumors, 13 thoracic metastases, 3 thymoma, 3 mesothelioma). At doses of 4-5 mg/kg, the TBR from primary NSCLC versus other malignancies was no different (2.70 vs. 3.21, P=1.00). At doses of 1-3 mg/kg, the TBR was greater for the non-NSCLCs (3.19 vs. 1.49, P=0.0006). Background fluorescence from the heart or ribs was observed in 1/16 cases at 1-2

Indocyanine Green–Guided Pediatric Tumor Resection: Approach, Utility, and Challenges

“…Proximity of the kidney did not preclude the optimal fluorescence of all included primary adrenal NBs (four patients). Moreover, ACT may require a different dosing or timing of ICG injection specific to this tumor biology for optimal imaging ( 22 , 27 ). Measures to decrease ambient light contamination of the NIR field may mitigate background noise; however, it is unknown if further reduction in the ICG dose would reduce background noise without decreasing tumor signal and potentially diminishing the tumor-to-background ratio for some tumors.…”

“…Preclinical and clinical studies suggest that the tumor-to-background fluorescence ratio is optimized when imaging is obtained 24 h after injecting the intravenous dye ( 2 , 21 , 22 ), However, for liver primary tumors, a 72-h window has been suggested by others to allow greater washout of ICG from the adjacent normal liver tissue and improve the ability to identify tumors ( 24 , 25 ). Adult trials have used 3–5 mg/kg ICG to optimize the tumor-to-background ratio, which is more than double the maximum FDA-approved pediatric dose.…”

Recent progress in sono-photodynamic cancer therapy: From developed new sensitizers to nanotechnology-based efficacy-enhancing strategies

“…ICG as a medical diagnostic agent has been approved by the U.S. Food and Drug Administration (FDA) 96 . Many studies employed ICG derivatives as useful platforms for design of NIR fluorescent probes 97 .…”

Unique Benefits of Tumor-Specific Nanobodies for Fluorescence Guided Surgery

“…It is thought that the molecules extravasate from leaky tumor vessels with disorganized venous and lymphatic drainage and remain retained in solid tumors. This principle has been exploited for visualization of pancreatic cancer, glioblastomas and a number of thoracic malignancies using the lipophilic dye, ICG [ 16 , 17 , 18 ]. A high dose of the dye is administered several days prior to imaging to allow slow accumulation in the tumors.…”