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

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, Pete C. Pieslor, Hung K. Cheung, Jos G. W. Kosterink, Elisabeth G. E. de Vries*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

19 Citations (Scopus)

Abstract

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 epsilon (CD3 epsilon) on T cells. We labeled AMG 110 with Zr-89 or near infrared fluorescent dye (IRDye) 800CW to study its tumor targeting and tissue distribution. Methods: Biodistribution and tumor uptake of Zr-89-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 Zr-89-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 Zr-89-AMG 110 can be clearly visualized using small-animal PET imaging up to 72 h after injection. The highest tumor uptake of Zr-89-AMG 110 at the 40-mu g 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 Zr-89-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 Zr-89 and IRDye 800CW to evaluate tumor and tissue uptake kinetics of bispecific T cell engager antibody constructs in preclinical and clinical settings.

Original languageEnglish
Pages (from-to)812-817
Number of pages6
JournalJournal of Nuclear Medicine
Volume57
Issue number5
DOIs
Publication statusPublished - May-2016

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