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86/90Y‑Labeled Monoclonal Antibody Targeting Tissue Factor for Pancreatic Cancer Theranostics
journal contribution
posted on 2020-03-31, 19:36 authored by Carolina
A. Ferreira, Emily B. Ehlerding, Zachary T. Rosenkrans, Dawei Jiang, Tuanwei Sun, Eduardo Aluicio-Sarduy, Jonathan W. Engle, Dalong Ni, Weibo CaiPancreatic
cancer is highly aggressive, with a median survival
time of less than 6 months and a 5-year overall survival rate of around
7%. The poor prognosis of PaCa is largely due to its advanced stage
at diagnosis and the lack of efficient therapeutic options. Thus,
the development of an efficient, multifunctional PaCa theranostic
system is urgently needed. Overexpression of tissue factor (TF) has
been associated with increased tumor growth, angiogenesis, and metastasis
in many malignancies, including pancreatic cancer. Herein, we propose
the use of a TF-targeted monoclonal antibody (ALT836) conjugated with
the pair 86/90Y as a theranostic agent against pancreatic
cancer. For methods, serial PET imaging with 86Y-DTPA-ALT836
was conducted to map the biodistribution the tracer in BXPC-3 tumor-bearing
mice. 90Y-DTPA-ALT836 was employed as a therapeutic agent
that also allowed tumor burden monitoring through Cherenkov luminescence
imaging. The results were that the uptake of 86Y-DTPA-ALT836
in BXPC-3 xenograft tumors was high and increased over time up to
48 h postinjection (p.i.), corroborated through ex vivo biodistribution studies and further confirmed by Cherenkov luminescence
Imaging. In therapeutic studies, 90Y-DTPA-ALT836 was found
to slow tumor growth relative to the control groups and had significantly
smaller (p < 0.05) tumor volumes 1 day p.i. Histological
analysis of ex vivo tissues revealed significant
damage to the treated tumors. The conclusion is that the use of the 86/90Y theranostic pair allows PET imaging with excellent tumor-to-background
contrast and treatment of TF-expressing pancreatic tumors with promising
therapeutic outcomes.
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86 Y-DTPA-ALT 836multifunctional PaCa theranostic systemBXPC -3 tumor-bearing micetumor burden monitoringpancreatic cancerPancreatic Cancer Theranostics Pancreatic cancerCherenkov luminescence ImagingPET imaging48 h postinjectionTF-expressing pancreatic tumorstumor growthBXPC -3 xenograft tumorsAntibody Targeting Tissue Factorvivo biodistribution studiesCherenkov luminescence imaging90 Y-DTPA-ALT 836
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