PT  - JOURNAL ARTICLE
AU  - Hao Hong
AU  - Yin Zhang
AU  - Tapas R. Nayak
AU  - Jonathan W. Engle
AU  - Hing C. Wong
AU  - Bai Liu
AU  - Todd E. Barnhart
AU  - Weibo Cai
TI  - Immuno-PET of Tissue Factor in Pancreatic Cancer
AID  - 10.2967/jnumed.112.105460
DP  - 2012 Nov 01
TA  - Journal of Nuclear Medicine
PG  - 1748--1754
VI  - 53
IP  - 11
4099  - http://jnm.snmjournals.org/content/53/11/1748.short
4100  - http://jnm.snmjournals.org/content/53/11/1748.full
SO  - J Nucl Med2012 Nov 01; 53
AB  - 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 64Cu. 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 64Cu-NOTA-ALT-836 to target TF in vivo. Results: There was no difference in TF binding affinity between ALT-836 and NOTA-ALT-836. 64Cu-labeling was achieved with high yield and specific activity. Serial PET revealed that the uptake of 64Cu-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 64Cu-NOTA-ALT-836. Conclusion: Herein we report the first successful PET imaging of TF expression. Persistent and TF-specific uptake of 64Cu-NOTA-ALT-836 was observed in pancreatic cancer models.