Background/Purpose:The only potentially curative procedure for pancreatic cancer is R0 resection, which is difficult to achieve due to poorly defined tumor margins. In the present study, we used an anti-CA19-9 antibody conjugated to a near-infrared fluorophore in orthotopic mouse models to target and visualize pancreatic cancer.Methods:Orthotopic models of the human pancreatic cancer cell lines SW1990 and BxPC3 were established by implanting tumor fragments into the pancreas of athymic nude mice. Anti-CA19-9 and control IgG were conjugated with IRDye800CW. Mice received 50 µg of CA19-9–IRDye800CW or IgG-IRDye800CW via tail-vein injection and were imaged after 72 h. MIA PaCa-2, a CA19-9-negative cell line, was used in subcutaneous models to assess targeting specificity.Results:Using the LI-COR Pearl imaging system in the SW1990 model, the tumor-to-pancreas ratio (TPR) was 4.51 (±0.74), and the tumor to the liver ratio (TLR) was 3.05 (±0.60) with CA19-9-IRDye800CW, while the TPR was 1.67 (±0.16) and the TLR was 0.95 (±0.05) for the non-specific control IgG–IRDye800CW. Using a clinically available fluorescence laparoscope, CA19-9-1RDye800CW demonstrated a TPR of 2.34 (±0.44) and a TLR of 2.23 (±0.49), compared to 1.11 (±0.13) and 0.69 (±0.07), respectively, for IgG-IRDye800CW in the SW1990 orthotopic model. In the BxPC3 models, the TPR was 3.82 (±0.55) and the TLR was 4.13 (±0.77) for CA19-9-IRDye800CW compared to 2.40 (±0.31) and 1.49 (±0.23), respectively, for IgG-IRDye800CW.Conclusions:CA19-9-IRDye800CW provided specific in vivo targeting of two human pancreatic cancer cell lines in orthotopic nude mouse models with superior TPRs and TLRs compared to IgG-IRDye800CW. This tumor-specific fluorescent CA19-9 antibody is a promising clinical tool for improved visualization of pancreatic cancer.
背景/目的：胰腺癌唯一可能根治的手术是R0切除，但由于肿瘤边界不清，实现这一目标较为困难。本研究采用近红外荧光染料标记的抗CA19-9抗体，在原位小鼠模型中实现对胰腺癌的靶向可视化。 方法：将人胰腺癌细胞系SW1990和BxPC3的肿瘤组织块植入无胸腺裸鼠胰腺内，建立原位模型。将抗CA19-9抗体和对照IgG与IRDye800CW荧光染料偶联。通过尾静脉注射给予小鼠50 µg CA19-9–IRDye800CW或IgG-IRDye800CW，72小时后进行成像。采用CA19-9阴性细胞系MIA PaCa-2建立皮下模型以评估靶向特异性。 结果：在SW1990模型中，使用LI-COR Pearl成像系统检测显示，CA19-9-IRDye800CW组的肿瘤与胰腺信号比（TPR）为4.51（±0.74），肿瘤与肝脏信号比（TLR）为3.05（±0.60）；而非特异性对照IgG–IRDye800CW组的TPR为1.67（±0.16），TLR为0.95（±0.05）。使用临床可用的荧光腹腔镜观察，在SW1990原位模型中，CA19-9-IRDye800CW组的TPR为2.34（±0.44），TLR为2.23（±0.49）；而IgG-IRDye800CW组分别为1.11（±0.13）和0.69（±0.07）。在BxPC3模型中，CA19-9-IRDye800CW组的TPR为3.82（±0.55），TLR为4.13（±0.77）；而IgG-IRDye800CW组分别为2.40（±0.31）和1.49（±0.23）。 结论：CA19-9-IRDye800CW在原位裸鼠模型中能够特异性靶向两种人胰腺癌细胞系，其TPR和TLR均显著优于IgG-IRDye800CW。这种肿瘤特异性荧光标记的CA19-9抗体有望成为改善胰腺癌术中可视化的临床工具。
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