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  • Title: Immuno-PET of tissue factor in pancreatic cancer.
    Author: Hong H, Zhang Y, Nayak TR, Engle JW, Wong HC, Liu B, Barnhart TE, Cai W.
    Journal: J Nucl Med; 2012 Nov; 53(11):1748-54. PubMed ID: 22988057.
    Abstract:
    UNLABELLED: Upregulation of tissue factor (TF) expression leads to increased patient morbidity and mortality in many solid tumor types. The goal of this study was to develop a PET tracer for imaging of TF expression in pancreatic cancer. METHODS: ALT-836, a chimeric antihuman TF monoclonal antibody, was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with (64)Cu. To compare the TF binding affinity of ALT-836 and NOTA-ALT-836, flow cytometry analysis was performed in 3 pancreatic cancer cell lines with different expression levels of TF (from low to high: PANC-1, ASPC-1, and BXPC-3). PET, biodistribution, blocking, and histology studies were performed on pancreatic tumor-bearing mice to evaluate the ability and specificity of (64)Cu-NOTA-ALT-836 to target TF in vivo. RESULTS: There was no difference in TF binding affinity between ALT-836 and NOTA-ALT-836. (64)Cu-labeling was achieved with high yield and specific activity. Serial PET revealed that the uptake of (64)Cu-NOTA-ALT-836 in BXPC-3 tumors (high TF expression) was 5.7 ± 1.8, 10.4 ± 0.8, and 16.5 ± 2.6 percentage injected dose per gram at 4, 24, and 48 h after injection, respectively (n = 4), significantly higher than that in the PANC-1 and ASPC-1 tumors. Biodistribution data as measured by γ-counting were consistent with the PET findings. Blocking experiments and histology further confirmed the TF specificity of (64)Cu-NOTA-ALT-836. CONCLUSION: Herein we report the first successful PET imaging of TF expression. Persistent and TF-specific uptake of (64)Cu-NOTA-ALT-836 was observed in pancreatic cancer models.
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