Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
PLoS One. 2013;8(4):e61230. doi: 10.1371/journal.pone.0061230. Epub 2013 Apr 5.
Pancreatic cancer is an aggressive cancer and its prognosis remains poor. Therefore, additional effective therapy is required to augment and/or complement current therapy. CD147, high expression in pancreatic cancer, is involved in the metastatic process and is considered a good candidate for targeted therapy. CD147-specfic imaging could be useful for selection of appropriate patients. Therefore, we evaluated the potential of a fully human anti-CD147 monoclonal antibody 059-053 as a new positron emission tomography (PET) probe for pancreatic cancer.
CD147 expression was evaluated in four pancreatic cancer cell lines (MIA Paca-2, PANC-1, BxPC-3, and AsPC-1) and a mouse cell line A4 as a negative control. Cell binding, competitive inhibition and internalization assays were conducted with (125)I-, (67)Ga-, or (89)Zr-labeled 059-053. In vivo biodistribution of (125)I- or (89)Zr-labeled 059-053 was conducted in mice bearing MIA Paca-2 and A4 tumors. PET imaging with [(89)Zr]059-053 was conducted in subcutaneous and orthotopic tumor mouse models.
Among four pancreatic cancer cell lines, MIA Paca-2 cells showed the highest expression of CD147, while A4 cells had no expression. Immunohistochemical staining showed that MIA Paca-2 xenografts also highly expressed CD147 in vivo. Radiolabeled 059-053 specifically bound to MIA Paca-2 cells with high affinity, but not to A4. [(89)Zr]059-053 uptake in MIA Paca-2 tumors increased with time from 11.0±1.3% injected dose per gram (ID/g) at day 1 to 16.9±3.2% ID/g at day 6, while [(125)I]059-053 uptake was relatively low and decreased with time, suggesting that 059-053 was internalized into tumor cells in vivo and (125)I was released from the cells. PET with [(89)Zr]059-053 clearly visualized subcutaneous and orthotopic tumors.
[(89)Zr]059-053 is a promising PET probe for imaging CD147 expression in pancreatic cancer and has the potential to select appropriate patients with CD147-expressing tumors who could gain benefit from anti-CD147 therapy.
胰腺癌是一种侵袭性癌症，其预后仍然较差。因此，需要额外的有效治疗方法来增强和/或补充现有治疗方法。CD147 在胰腺癌中高表达，参与转移过程，被认为是靶向治疗的良好候选物。CD147 特异性成像可能有助于选择合适的患者。因此，我们评估了全人源抗 CD147 单克隆抗体 059-053 作为一种新的正电子发射断层扫描（PET）探针用于胰腺癌的潜力。
在四种胰腺癌细胞系（MIA Paca-2、PANC-1、BxPC-3 和 AsPC-1）和一种小鼠细胞系 A4 中评估 CD147 的表达情况，A4 作为阴性对照。用（125）I-、（67）Ga-或（89）Zr 标记的 059-053 进行细胞结合、竞争抑制和内化测定。在携带 MIA Paca-2 和 A4 肿瘤的小鼠中进行（125）I-或（89）Zr 标记的 059-053 的体内生物分布研究。用 [(89)Zr]059-053 进行皮下和原位肿瘤小鼠模型的 PET 成像。
在四种胰腺癌细胞系中，MIA Paca-2 细胞表达 CD147 的水平最高，而 A4 细胞则没有表达。免疫组织化学染色显示，MIA Paca-2 异种移植瘤在体内也高度表达 CD147。放射性标记的 059-053 特异性地与 MIA Paca-2 细胞高亲和力结合，但与 A4 细胞不结合。[(89)Zr]059-053 在 MIA Paca-2 肿瘤中的摄取随时间增加，从第 1 天的 11.0±1.3%注入剂量/克（ID/g）增加到第 6 天的 16.9±3.2% ID/g，而 [(125)I]059-053 的摄取相对较低且随时间下降，这表明 059-053 在体内被内化到肿瘤细胞中，而（125）I 从细胞中释放出来。用 [(89)Zr]059-053 进行的 PET 清晰地可视化了皮下和原位肿瘤。
[(89)Zr]059-053 是一种有前途的用于成像胰腺癌中 CD147 表达的 PET 探针，有可能选择具有 CD147 表达肿瘤的合适患者，这些患者可能从抗 CD147 治疗中获益。
