Evaluating the utility of ICG-based NIR imaging for small intestine neuroendocrine tumors: Challenges and the need for tumor-specific tracers

Purpose Accurate intraoperative localization of small intestinal neuroendocrine tumors (SI-NETs) remains a surgical challenge, with standard staging protocols frequently missing small primary or metastatic lesions. ICG has shown utility in other highly vascularized tumors, including pituitary and pancreatic neuroendocrine tumors and non-small cell lung cancer. We conducted a prospective feasibility study to evaluate the potential of near-infrared (NIR) fluorescence imaging (FI) using indocyanine green (ICG) to enhance intraoperative detection of SI-NETs. Methods The initial aim was to include at least 26 patients; however, after analysis of the first two patients, we decided to terminate the study prematurely. Therefore, we present data from two patients who underwent abdominal surgery. Each patient received 2.5 mg/kg of ICG intravenously 18 h before surgery, utilizing the second-window ICG (SWIG) technique. Intraoperative imaging was performed using the Quest Spectrum V2 camera system. The primary endpoint was fluorescence positivity of primary tumors, defined as a tumor-to-background ratio (TBR) ≥ 1.5. Results All primary tumors (n = 2) were identified via palpation and inspection, but none were fluorescence positive (median TBR 0.67, range 0.47–0.87). No occult primary or metastatic lesions were detected by fluorescence imaging. Metastatic lymph nodes and peritoneal nodules (n = 3, confirmed malignant) were also fluorescence negative. Strong non-specific background signal was observed in bowel and liver tissue, reflecting non-tumor-specific ICG uptake. Based on low tumor contrast and expert consensus, the study was terminated early without dose escalation. Conclusion These findings demonstrate that ICG-based NIR FI did not enhance intraoperative detection of SI-NETs or metastases in this feasibility cohort and is limited by non-specific background fluorescence. Our data suggest that passive EPR-based accumulation may not be sufficient for reliable visualization of SI-NETs. Our results underscore the need for tumor-specific tracers targeting neuroendocrine markers to improve surgical precision in SI-NETs.