Imaging and biodistribution of Her2/neu expression in non-small cell lung cancer xenografts with 64Cu-labeled trastuzumab PET
Imaging and biodistribution of Her2/neu expression in non-small cell lung cancer xenografts with 64Cu-labeled trastuzumab PET
复制标题
DOI：
10.1111/j.1349-7006.2010.01480.x
复制
发表时间：
2010-04-01
期刊：
影响因子：
5.7
通讯作者：
Endo, Keigo
中科院分区：
文献类型：
--
作者：
Paudyal, Pramila;Paudyal, Bishnuhari;Endo, Keigo
非小细胞肺癌（NSCLC）在大约59%的病例中过表达Her 2/neu基因。曲妥珠单抗是一种人源化单克隆抗体，可干扰Her 2信号传导，并被批准用于治疗Her 2/neu过表达的乳腺癌。然而，其在Her 2/neu过表达NSCLC中的治疗用途仍然不清楚。本研究旨在确定64 Cu标记的曲妥珠单抗正电子发射断层扫描（PET）在NSCLC中Her 2/neu表达的非侵入性成像中的作用。曲妥珠单抗与双功能螯合剂1，4，7，10-四氮杂环十二烷-1，4，7，10-四乙酸（DOTA）缀合并用Cu-64放射性标记。在Her 2/neu过表达（NCI-H2170）和阴性表达（NCI-H520）的NSCLC细胞系中测定DOTA-曲妥珠单抗的分子特异性。用64 Cu-DOTA-曲妥珠单抗PET和64 Cu-DOTA-IgG在携带NCI-H2170肿瘤的小鼠中进行Her 2/neu表达的成像。体外研究揭示了DOTA-曲妥珠单抗在Her 2/neu阳性NCI-H2170细胞中的特异性结合，而在Her 2/neu阴性NCI-H520细胞系中未观察到结合。生物分布和PET研究显示，在注射后24和48小时，64 CuDOTA-曲妥珠单抗在Her 2/neu过表达的NCI-H2170肿瘤中显著高积累（分别为21.4 +/- 1.4%和23.2 +/- 5.1%注射剂量/克（% ID/g））。Her 2/neu阴性NCI-H520肿瘤的PET成像显示64 CuDOTA-曲妥珠单抗的摄取少得多（4.0%ID/g）。64 Cu-DOTA-曲妥珠单抗的NCI-H2170肿瘤摄取显著高于64 Cu-DOTA-IgG（P < 0.0001）。64 Cu-DOTA-曲妥珠单抗显示出非常清晰的Her 2/neu阳性肿瘤图像，并且似乎作为PET示踪剂用于NSCLC中Her 2/neu基因表达的成像是有效的，这表明其潜在的临床用途用于鉴定可能从基于曲妥珠单抗的治疗中受益的患者。（Cancer Sci 2010; 101：1045-1050）
Non-small cell lung carcinomas (NSCLC) overexpress the Her2/neu gene in approximately 59% of cases. Trastuzumab, a humanized monoclonal antibody, interferes with Her2 signaling and is approved for the treatment of Her2/neu overexpressing breast cancer. However, its therapeutic use in Her2/neu overexpressing NSCLC remains obscure. The present study aimed to determine the role of 64 Cu-labeled trastuzumab positron emission tomography (PET) for non-invasive imaging of Her2/neu expression in NSCLC. Trastuzumab was conjugated with the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with Cu-64. The molecular specificity of DOTA-trastuzumab was determined in NSCLC cell lines with Her2/neu overexpression (NCI-H2170) and negative expression (NCI-H520). Imaging of Her2/neu expression was performed in NCI-H2170 tumor-bearing mice with 64 Cu-DOTA-trastuzumab PET and 64 Cu-DOTA-IgG. In vitro studies revealed specific binding of DOTA-trastuzumab in the Her2/neu positive NCI-H2170 cells, while no binding was seen in the Her2/neu negative NCI-H520 cell line. Biodistribution and PET studies revealed a significantly high accumulation of 64 CuDOTA-trastuzumab in the Her2/neu overexpressing NCI-H2170 tumor at 24 and 48 h post-injection (21.4 +/- 1.4% and 23.2 +/- 5.1% injection dose/gram (% ID/g), respectively). PET imaging of Her2/neu negative NCI-H520 tumors showed much less uptake of 64 CuDOTA- trastuzumab (4.0% ID/g). The NCI-H2170 tumor uptake of 64 Cu-DOTA-trastuzumab was significantly higher than that of 64 Cu-DOTA-IgG (P < 0.0001). 64 Cu-DOTA-trastuzumab showed a very clear image of a Her2/neu positive tumor and appeared to be effective as a PET tracer for imaging of Her2/neu gene expression in NSCLC, suggesting its potential clinical use for identifying patients that might benefit from trastuzumab-based therapy. (Cancer Sci 2010; 101: 1045-1050)