Surgical oncology · 2026
Evaluating the utility of ICG-based NIR imaging for small intestine neuroendocrine tumors: Challenges and the need for tumor-specific tracers.
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Dalmeijer Sebastiaan W R, Zweedijk Bo E, Boldewijn Danielle F, Galema Hidde A, van Ginhoven Tessa M, Franssen Gaston J H, van Velthuysen Marie-Louise, Grünhagen Dirk J, Verhoef Cornelis, Vahrmeijer Alexander L, Hilling Denise E, Keereweer Stijn
Аннотация
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.
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.