荧光抗 MUC5AC 可在患者来源的原位异种移植中特异性靶向胰腺癌。
Fluorescent Anti-MUC5AC Brightly Targets Pancreatic Cancer in a Patient-derived Orthotopic Xenograft.
机构信息
Department of Surgery, University of California San Diego, La Jolla, CA, U.S.A.
VA San Diego Healthcare System, San Diego, CA, U.S.A.
出版信息
In Vivo. 2022 Jan-Feb;36(1):57-62. doi: 10.21873/invivo.12676.
Abstract
BACKGROUND
Overexpression of mucin-5AC (MUC5AC) makes it a targetable biomarker in pancreatic cancer. The present study evaluated tumor targeting with a MUC5AC antibody conjugated to a near-infrared dye in a patient-derived orthotopic xenograft (PDOX) mouse model.
MATERIALS AND METHODS
MUC5AC monoclonal antibody was conjugated to the near-infrared dye IRDye800CW to synthesize MUC5AC-IR800. PDOX models were established by implanting a high-MUC5AC-expressing patient-derived pancreatic tumor on the pancreas of nude mice. After 4 weeks of PDOX tumor growth, mice were imaged after receiving MUC5AC-IR800 (75 μg) intravenously.
RESULTS
In the PDOX models, MUC5AC-IR800 selectively and brightly targeted the pancreatic tumor (tumor to background ratio: 2.46±0.465).
CONCLUSION
MUC5AC-IR800 provides distinct visualization of pancreatic tumors. MUC5AC-IR800 may be used clinically in the future to improve pancreatic cancer resection. This novel fluorescent probe is also promising for targeting of pre-malignant pancreatic lesions with subsequent resection under fluorescence guidance.
摘要
背景
黏蛋白-5AC（MUC5AC）的过表达使其成为胰腺癌的一个可靶向生物标志物。本研究评估了在患者来源的原位异种移植（PDOX）小鼠模型中，与近红外染料偶联的 MUC5AC 抗体的肿瘤靶向性。
材料和方法
将 MUC5AC 单克隆抗体与近红外染料 IRDye800CW 偶联，合成 MUC5AC-IR800。通过将高表达 MUC5AC 的患者来源胰腺肿瘤植入裸鼠胰腺中，建立 PDOX 模型。在 PDOX 肿瘤生长 4 周后，静脉注射 75μg MUC5AC-IR800 后对小鼠进行成像。
结果
在 PDOX 模型中，MUC5AC-IR800 选择性地、明亮地靶向胰腺肿瘤（肿瘤与背景比：2.46±0.465）。
结论
MUC5AC-IR800 为胰腺肿瘤提供了清晰的可视化效果。MUC5AC-IR800 未来可能在临床上用于改善胰腺癌切除术。这种新型荧光探针也有望用于荧光引导下对癌前胰腺病变进行靶向切除。
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