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Immuno-PET of tissue factor in pancreatic cancer.

ABSTRACT: 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.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.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 ?-counting were consistent with the PET findings. Blocking experiments and histology further confirmed the TF specificity of (64)Cu-NOTA-ALT-836.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.

SUBMITTER: Hong H

PROVIDER: S-EPMC3489969 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Immuno-PET of tissue factor in pancreatic cancer.

Hong Hao H Zhang Yin Y Nayak Tapas R TR Engle Jonathan W JW Wong Hing C HC Liu Bai B Barnhart Todd E TE Cai Weibo W

Journal of nuclear medicine : official publication, Society of Nuclear Medicine 20120917 11

<h4>Unlabelled</h4>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.<h4>Methods</h4>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 NOT ...[more]

PMID: 22988057

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Immuno-PET of tissue factor in pancreatic cancer.

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Immuno-PET of tissue factor in pancreatic cancer.

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