TY - JOUR
T1 - Biodistribution and PET Imaging of Labeled Bispecific T Cell-Engaging Antibody Targeting EpCAM
AU - Warnders, Frank J.
AU - Waaijer, Stijn J. H.
AU - Pool, Martin
AU - Lub-de Hooge, Marjolijn N.
AU - Friedrich, Matthias
AU - Terwisscha van Scheltinga, Anton G. T.
AU - Deegen, Petra
AU - Stienen, Sabine K.
AU - Pieslor, Pete C.
AU - Cheung, Hung K.
AU - Kosterink, Jos G. W.
AU - de Vries, Elisabeth G. E.
N1 - Copyright © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.
PY - 2016/5
Y1 - 2016/5
N2 - 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.
AB - 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.
U2 - 10.2967/jnumed.115.168153
DO - 10.2967/jnumed.115.168153
M3 - Article
C2 - 26848172
VL - 57
SP - 812
EP - 817
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
SN - 0161-5505
IS - 5
ER -