Biodistribution and PET Imaging of Labeled Bispecific T Cell-Engaging Antibody Targeting EpCAM.

Abstract

UNLABELLED:

AMG 110, a bispecific T cell engager (BiTE) antibody construct, induces T cell-mediated cancer cell death by cross-linking epithelial cell adhesion molecule (EpCAM) on tumor cells with a cluster of differentiation 3 ε (CD3ε) on T cells. We labeled AMG 110 with (89)Zr or near-infrared fluorescent dye (IRDye) 800CW to study its tumor targeting and tissue distribution.

METHODS:

Biodistribution and tumor uptake of (89)Zr-AMG 110 was studied up to 6 d after intravenous administration to nude BALB/c mice bearing high EpCAM-expressing HT-29 colorectal cancer xenografts. Tumor uptake of (89)Zr-AMG 110 was compared with uptake in head and neck squamous cell cancer FaDu (intermediate EpCAM) and promyelocytic leukemia HL60 (EpCAM-negative) xenografts. Intratumoral distribution in HT-29 tumors was studied using 800CW-AMG 110.

RESULTS:

Tumor uptake of (89)Zr-AMG 110 can be clearly visualized using small-animal PET imaging up to 72 h after injection. The highest tumor uptake of (89)Zr-AMG 110 at the 40-μg dose level was observed at 6 and 24 h (respectively, 5.35 ± 0.22 and 5.30 ± 0.20 percentage injected dose per gram; n = 3 and 4). Tumor uptake of (89)Zr-AMG 110 was EpCAM-specific and correlated with EpCAM expression. 800CW-AMG 110 accumulated at the tumor cell surface in viable EpCAM-expressing tumor tissue.

CONCLUSION:

PET and fluorescent imaging provided real-time information about AMG 110 distribution and tumor uptake in vivo. Our data support using (89)Zr and IRDye 800CW to evaluate tumor and tissue uptake kinetics of bispecific T cell engager antibody constructs in preclinical and clinical settings.

• Authors: Frank J Warnders, Stijn J H Waaijer, Martin Pool, Marjolijn N Lub-de Hooge, Matthias Friedrich, Anton G T Terwisscha van Scheltinga, Petra Deegen, Sabine K Stienen, Peter C Pieslor, H Kam Cheung, Jos G W Kosterink, Elisabeth G E de Vries
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 57 Issue 5 Pg. 812-7 (05 2016) ISSN: 1535-5667 [Electronic] United States
• PMID: 26848172 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Chemical References

• Antibodies, Monoclonal
• Epithelial Cell Adhesion Molecule
• Radioisotopes
• Zirconium

Topics

• Animals
• Antibodies, Monoclonal (immunology, pharmacokinetics)
• Epithelial Cell Adhesion Molecule (immunology)
• HL-60 Cells
• HT29 Cells
• Humans
• Isotope Labeling
• Male
• Mice
• Positron-Emission Tomography (methods)
• Radioisotopes
• T-Lymphocytes (immunology)
• Tissue Distribution
• Zirconium