Abstract Background: 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 node. The aim of this study was to evaluate the effectiveness of indocyanine green-neomannosyl human serum albumin (MSA:ICG) which targets macrophage mannose receptor CD206 for SLN mapping. Methods: LN targeting ability was examined on mouse footpad models of uterine cancer using MSA:ICG and ICG for comparison. Seven mice with uterine cancer and 2 mice without cancer as a control group were each assigned to MSA:ICG and ICG groups. After injection of tracers, fluorescence images were taken and SLN biopsy was done to confirm LN metastasis status. We compared the signal-to-background ratio (SBR) according to time. Results: In both MSA:ICG and ICG group, 16 lymph nodes out of 18 were detected using fluorescence imaging (detection rate: 88.9%). Four lymph nodes in MSA:ICG group and 5 lymph nodes in ICG group were metastatic among 16 lymph node each group. Excluding lymph nodes that were not detected, the SBR after the injection of MSA:ICG group was significantly higher than ICG group in metastatic LN (MSA:ICG 4.36 vs ICG 3.07, p<0.001), non-metastatic lymph nodes (MSA:ICG 3.11 vs ICG 1.93, p=0.001), and normal control lymph nodes (MSA:ICG 1.38 vs ICG 0.54, p<0.001). Comparing signal intensity according to CD206 expression, there was no difference in SBR values between the two groups in patients without CD206 expression, but the MSA group had a statistically significantly higher SBR value than the ICG group (p<0.001) in patients with CD206 moderate or high expression. Conclusions: This study showed that MSA:ICG may be an effective tracer for sentinel lymph node mapping. In addition, the metastatic lymph nodes expressing CD206 showed higher signal than normal lymph nodes in MSA:ICG group, unlike in ICG group. Further studies using larger animal models and clinical trials are needed to confirm this result. Citation Format: Hyun-Woong Cho, OK Hwa Jeon, Sanghoon Lee, Hyun Koo Kim, Jae Kwan Lee, Jin Hwa Hong. Targeting mannose receptor expression on macrophages for sentinel lymph node mapping in endometrial cancer: murine model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2385.
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