Sentinel lymph node mapping in uterine cancer via indocyanine green-neomannosyl human serum albumin: In vivo mouse model

Abstract

Objectives Sentinel lymph node (SLN) mapping has been used in various cancer surgery, including endometrial cancer, as a targeted assessment tool for identifying lymph node metastases, an alternative for complete lymphadenectomy to minimize surgical morbidity. Neomannosyl human serum albumin (MSA) targets the macrophage mannose receptor, CD206, which is highly expressed in metastatic lymph nodes. The aim of this study was to evaluate the effectiveness of indocyanine green-neomannosyl human serum albumin (ICG-MSA), which targets macrophage mannose receptor CD206 for SLN mapping.

Methods LN targeting ability was examined on mouse footpad models of uterine cancer using ICG-MSA and ICG for comparison. Seven mice with uterine cancer and 2 mice without cancer as a control group were each assigned to ICG-MSA and ICG. After injecting tracers, fluorescence images were taken, and an SLN biopsy was done to confirm LN metastasis status. We compared the signal-to-background ratio (SBR) according to time.

Results In the ICG-MSA group, 16 lymph nodes out of 18 were detected using fluorescence imaging, and 15 lymph nodes out of 18 were mapped in the ICG group. Four lymph nodes in the ICG-MSA group and 5 lymph nodes in the ICG group were metastatic, whereas 8 lymph nodes in the ICG-MSA group and 7 lymph nodes in the ICG group were non-metastatic. Four lymph nodes in the ICG-MSA group and 4 lymph nodes in the ICG group were normal. Excluding lymph nodes that were not detected, the SBR after the injection of the ICG-MSA group was significantly higher than ICG group in metastatic LN (ICG-MSA: 4.36; ICG: 3.07, P = 0.0099), non-metastatic LN (ICG-MSA: 3.11; ICG: 1.93, P = 0.0013), and normal control LN (ICG-MSA: 1.38; ICG: 0.54, P = 0.0006). We also compared the SBR of ICG and MSA-ICG according to the expression level of CD206, and MSA-ICG showed significantly higher SBR as the CD206 expression level increased when ICG showed no difference.

Conclusions ICG-MSA proved to be an effective tracer for lymph node detection compared to ICG. It also showed a significant signal-to-background ratio difference between metastatic and non-metastatic lymph nodes, which would be useful in oncologic surgery. Further studies using larger models and clinical trials are needed to confirm this result.