Imaging and biodistribution of Her2/neu expression in non-small cell lung cancer xenografts with 64Cu-labeled trastuzumab PET

被引：43

作者：

Paudyal, Pramila ^{[1
,2
]}

Paudyal, Bishnuhari ^{[1
,2
]}

Hanaoka, Hirofumi

Oriuchi, Noboru ^{[1
,2
]}

Iida, Yashuhiko

Yoshioka, Hiroki ^{[1
,2
]}

Tominaga, Hideyuki ^{[1
,2
]}

Watanabe, Satoshi ^{[3
]}

Watanabe, Shigeki ^{[3
]}

Ishioka, Noriko S. ^{[3
]}

Endo, Keigo ^{[1
,2
]}

机构：

[1] Gunma Univ, Grad Sch Med, Dept Diagnost Radiol, Maebashi, Gunma, Japan

[2] Gunma Univ, Grad Sch Med, Dept Nucl Med, Maebashi, Gunma, Japan

[3] Japan Atom Energy Agcy, Quantum Beam Sci Directorate, Takasaki, Gunma, Japan

来源：

CANCER SCIENCE | 2010年 / 101卷 / 04期

关键词：

PHASE-II TRIAL; BREAST-CANCER; ANTIBODY; GEMCITABINE; CISPLATIN; MICE;

D O I：

10.1111/j.1349-7006.2010.01480.x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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)

引用

页码：1045 / 1050

页数：6

共 35 条

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