RT Journal Article
SR Electronic
T1 Immuno-PET of Tissue Factor in Pancreatic Cancer
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1748
OP 1754
DO 10.2967/jnumed.112.105460
VO 53
IS 11
A1 Hong, Hao
A1 Zhang, Yin
A1 Nayak, Tapas R.
A1 Engle, Jonathan W.
A1 Wong, Hing C.
A1 Liu, Bai
A1 Barnhart, Todd E.
A1 Cai, Weibo
YR 2012
UL http://jnm.snmjournals.org/content/53/11/1748.abstract
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.