Small-Animal PET Imaging of Pancreatic Cancer Xenografts Using a 64Cu-Labeled Monoclonal Antibody, MAb159.
Small-Animal PET Imaging of Pancreatic Cancer Xenografts Using a 64Cu-Labeled Monoclonal Antibody, MAb159.
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DOI：
10.2967/jnumed.115.155812
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发表时间：
2015-06
期刊：
影响因子：
--
通讯作者：
Li Z
中科院分区：
文献类型：
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作者：
Wang H;Li D;Liu S;Liu R;Yuan H;Krasnoperov V;Shan H;Conti PS;Gill PS;Li Z
细胞表面GRP78受体的过度表达与肿瘤的生长、转移和耐药有关。我们基于一种新的抗GRP78的单抗MAb159，研制了一种用于肿瘤GRP78表达的正电子发射计算机断层显像的64Cu标记的探针。通过抗体上的赖氨酸将MAb159与64Cu螯合剂DOTA偶联。DOTA-人免疫球蛋白也被制备为不与GRP78结合的对照。在裸鼠BXPC3胰腺癌移植瘤中对所得的PET探针进行了评价。合成的放射性示踪剂的比活度为0.8MBq/μg抗体。在BXPC3移植瘤中，64Cu-DOTA-MAb159有明显的肿瘤聚集(注射后第1、17、48天每克注射剂量百分比分别为4.3±1.2、15.4±2.6和18.3±1.0)。相比之下，64CuDOTA人免疫球蛋白具有较低的BXPC3肿瘤蓄积量(注射后1、17、48h每克注射剂量百分比分别为4.8±0.5、7.5±0.7和4.6±0.8%)。我们证明GRP78可以作为胰腺癌显像的有效靶点。这种方法的成功将对在抗GRP78治疗的早期阶段评估病程和治疗效果具有重要价值。此外，这些新开发的探针可能在其他类型的癌症中有重要的应用，过度表达GRP78。
Overexpression of the GRP78 receptor on cell surfaces has been linked with tumor growth, metastasis, and resistance to therapy. We developed a 64Cu-labeled probe for PET imaging of tumor GRP78 expression based on a novel anti-GRP78 monoclonal antibody, MAb159. MAb159 was conjugated with the 64Cu-chelator DOTA through lysines on the antibody. DOTA–human IgG was also prepared as a control that did not bind to GRP78. The resulting PET probes were evaluated in BXPC3 pancreatic cancer xenografts in athymic nude mice. The radiotracer was synthesized with a specific activity of 0.8 MBq/μg of antibody. In BXPC3 xenografts, 64Cu-DOTA-MAb159 demonstrated prominent tumor accumulation (4.3 ± 1.2, 15.4 ± 2.6, and 18.3 ± 1.0 percentage injected dose per gram at 1, 17, and 48 after injection, respectively). In contrast, 64Cu-DOTA–human IgG had low BXPC3 tumor accumulation (4.8 ± 0.5, 7.5 ± 0.7, and 4.6 ± 0.8 percentage injected dose per gram at 1, 17, and 48 h after injection, respectively). We demonstrated that GRP78 can serve as a valid target for pancreatic cancer imaging. The success of this approach will be valuable for evaluating disease course and therapeutic efficacy at the earliest stages of anti-GRP78 treatment. Moreover, these newly developed probes may have important applications in other types of cancer overex-pressing GRP78.