mp6b01130_si_001.pdf (3.83 MB)
Preloading with Unlabeled CA19.9 Targeted Human Monoclonal Antibody Leads to Improved PET Imaging with 89Zr-5B1
journal contribution
posted on 2017-02-13, 00:00 authored by Jacob
L. Houghton, Dalya Abdel-Atti, Wolfgang W. Scholz, Jason S. LewisCA19.9
is one of the most commonly occurring and highest density
antigens in >90% of pancreatic cancers, making it an excellent
target
for monoclonal antibody (mAb)-based imaging and therapy applications.
Preloading of unlabeled antibodies to enhance targeting of a radiolabeled
mAb has been previously described both for imaging and radioimmunotherapy
studies for other targets. We investigated the effect of preloading
with the unmodified anti-CA19.9 antibody 5B1 on the uptake and contrast
of the PET tracer 89Zr-5B1 in subcutaneous and orthotopic
murine models of pancreatic cancer utilizing Capan-2 xenografts, known
to both express CA19.9 and shed antigen into circulation. Biodistribution
and PET imaging studies with 89Zr-5B1 alone showed high
levels in the liver, spleen, and lymph nodes of mice with subcutaneous
Capan-2 tumor xenografts when administered without preinjection of
5B1. When unlabeled 5B1 was administered prior to 89Zr-5B1,
the tracer significantly enhanced image contrast and tumor to tissue
ratios in the same model, and the improvement was related to the time
interval between the injections. Moreover, tumors were clearly delineated
in an orthotopic pancreatic cancer model using our optimized approach.
Taken together, these data suggest that preloading with 5B1 can improve 89Zr-5B1 imaging of disease in a Capan-2 mouse model and that
exploration of preloading may have clinical utility for ongoing clinical
investigations.
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Preloadingdensity antigenstime intervalradiolabeled mAbradioimmunotherapy studiesanti-CA 19.9 antibody 5 B 15 B 1.image contrastPET Imagingpancreatic cancerpreloadingsubcutaneous Capan -2 tumor xenografts89 Zr -5B imagingCapan -2 xenograftsCapan -2 mouse modelPET imaging studies89 Zr -5B CA 19.9therapy applicationslymph nodesUnlabeled CA 19.9 Targeted HumanCA 19.9optimized approach89 Zr -5Borthotopic pancreatic cancer modeltissue ratiosorthotopic murine modelsPET tracer 89 Zr -5B5 B 1pancreatic cancers
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