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 L ung cancer is one of the world's leading causes of death, with a 5-year survival rate of less than 10%.(1) Activation of ras genes and human epidermal growth factor receptor 2 (Her2/neu) genes is encountered in subpopulations of non-small cell lung carcinoma (NSCLC) patients and has been linked to shortened survival. Overexpression of the Her2/neu gene is closely associated with intrinsic multiple drug resistance in NSCLC cell lines.(2) Her2/neu is a transmembrane tyrosine kinase belonging to the surface receptor family. It does not bind ligand but instead acts as a preferred heterodimerization partner for ligand-activated sibling members to amplify mitotic signaling. Trastuzumab, a humanized monoclonal antibody that targets Her2/neu, inhibits neoplastic cell proliferation both in vitro and in vivo.(4) In breast cancer, overexpression of Her2/neu is seen in 40% of cases, and its activation follows heterodimerization with a member of the EGFR family and triggers important biological effects such as proliferation, migration and differentiation.(5) Trastuzumab significantly increases the survival of patients with advanced metastatic breast cancer. Overexpression of Her2/neu is reported in up to 59% of cases of NSCLC and the 2+/3+ overexpression rate is 5-20% in adenocarcinomas.(8-10) As in breast cancer, studies have suggested that the overexpression of Her2/neu in NSCLC is associated with a worse prognosis than negative expression of Her2/ neu. (11,12) The role of trastuzumab targeting Her2/neu expression in the NSCLC has been largely marginalized. Even though NSCLC is usually chemoresistant, the synergistic effect between trastuzumab and chemotherapeutic agents was found to be greater in Her2/neu positive NSCLC than in breast cancer cell lines. (13,14) NSCLC patients with Her2/neu overexpression (3+) in immunohistochemistry (IHC) had better survival when treated with trastuzumab-based therapy than the overall population, but only a small percentage of patients benefited.(10) The marked variation in functional anatomy and pathophysiology within human tumors and within individual patients may account for the high va...

Vascular endothelial growth factor (VEGF) is considered to be a major angiogenic factor responsible for the development of tumor vasculature. The aim of this study was to image VEGF expression with 64 Cu-labeled anti-VEGF antibody (bevacizumab) non-invasively, and to see whether or not the expression was correlated with tumor accumulation in colorectal cancer xenografts. Bevacizumab was conjugated with the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with 64 Cu. In vivo biodistribution studies and positron emission tomography (PET) imaging were performed on mice bearing human colorectal cancer (HT29) xenografts after injection of 64 Cu-DOTA-bevacizumab, which showed clear accumulation of 64 Cu-DOTA-bevacizumab in the tumor (22.7 ± 1.0 %ID ⁄ g, 24 ± 0.2 %ID ⁄ g, 19.0 ± 2.5 %ID ⁄ g at 24, 48 and 72 h, respectively). Tumor accumulation of 64 Cu-DOTA-bevacizumab was significantly correlated with VEGF expression as measured by western blot (q = 0.81, P = 0.004). Vascular endothelial growth factor blocking with unlabeled bevacizumab significantly reduced tumor accumulation of 64 Cu-DOTA-bevacizumab (9.7 ± 1.2 %ID ⁄ g, P < 0.001) at 48 h. Interestingly, the blood concentration of VEGF in the mice treated with excess fold of bevacizumab was significantly higher than those without at 48 h (25.5 ± 4.6 %ID ⁄ g vs 6.5 ± 2.1 %ID ⁄ g, P = 0.0016). Liver uptake decreased from 24 h (17.2 ± 1.7 %ID ⁄ g) to 48 h (13.0 ± 4.2 %ID ⁄ g) and 72 h (10.6 ± 1.5 %ID ⁄ g) due to hepatic clearance of the tracer. The present study successfully showed 64 Cu-DOTA-bevacizumab as a potential PET tracer for noninvasive imaging of VEGF expression in colorectal cancer xenografts. (Cancer Sci 2011; 102: 117-121) V ascular endothelial growth factor (VEGF) is considered to be a major angiogenic factor responsible for the development of the tumor vasculature network having leaky blood vessels and insufficient blood flow and high interstitial blood pressure. Because almost all kinds of tumor progression is dependent on angiogenesis, it has gained a lot of interest among scientists to search for antiangiogenic molecules and to design antiangiogenic strategies for cancer treatment and the prevention of cancer recurrence or metastasis.(1-3) Bevacizumab, a humanized monoclonal antibody, binds to all VEGF isoforms and thereby prevents interaction with its receptor tyrosine kinase VEGFR-1 and VEGFR-2, thus blocking VEGF-induced endothelial cell proliferation, permeability, survival and growth. (4,5) In animal models, administration of bevacizumab blocked the growth of human tumor xenografts and reduced the size and number of metastases.(6) Hurwitz et al.found that adding bevacizumab in combination with chemotherapy improved survival and produced consistent results across all patient subgroups with metastatic colorectal cancer (mCRC). Kabbinavar et al. Despite these promising results of bevacizumab-based therapy, selection of the right patients for bevacizumab-based treatment is a vit...

Cholangiocellular carcinoma (CCC) has been reported to have a high glucose uptake; however, the mechanism of glucose entry into these cells is still unclear. We investigated the relationship between

The therapeutic efficacy of RIT seems to largely depend on the tumor radiosensitivity.

Combined PET/CT showed improved diagnostic performance than PET alone by decreasing the number of false positive findings in patients with initial staging and follow up of head and neck malignancy.