Open AccessImaging and biodistribution of Her2/neu expression in non‐small cell lung cancer xenografts with 64 Cu‐labeled trastuzumab PET
Author(s) -
Paudyal Pramila,
Paudyal Bishnuhari,
Hanaoka Hirofumi,
Oriuchi Noboru,
Iida Yashuhiko,
Yoshioka Hiroki,
Tominaga Hideyuki,
Watanabe Satoshi,
Watanabe Shigeki,
Ishioka Noriko S,
Endo Keigo
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01480.x
Subject(s) - trastuzumab , dota , biodistribution , her2/neu , medicine , cancer research , monoclonal antibody , positron emission tomography , immunohistochemistry , breast cancer , cancer , in vitro , antibody , chemistry , nuclear medicine , pathology , immunology , chelation , biochemistry , organic chemistry
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 64 Cu. 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 Cu‐DOTA‐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 Cu‐DOTA‐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)