Molecular imaging of CEACAM6 using antibody probes of different sizes

Wednesday, October 26, 2011 — Poster Session III
10:00 a.m. – Noon	Natcher Conference Center	NIBIB	IMAG-28

Authors

• G Niu
• Y Murad
• H Gao
• O Jacobson
• J Zhang
• X Chen

Abstract

Carcinocinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is overexpressed in a number of human malignancies, especially in pancreatic cancer. In this study, we labeled anti-CEACAM6 antibodies of different sizes with 64Cu to image the CEACAM6 expression in xenograft pancreatic tumors and biodistribution of antibodies in vivo. Methods: Three antibodies specifically against CEACAM6 including a single-domain antibody 2A3 (16 kDa), a heavy chain antibody 2A3-mFc (80 kDa) and a full length antibody 9A6 (150 kDa) were used. The antibodies were conjugated with FITC and Cy5.5 for in vitro and ex vivo immunostaining and DOTA for further 64Cu labeling. Xenograft tumor models were developed BxPC3 human pancreatic cancer cell line that has high level of CEACAM6 expression. Results: 64Cu-DOTA-2A3 showed low tumor uptake and fast clearance on PET images. BxPC3 tumors were clearly visualized with 64Cu-DOTA-2A3mFc and 64Cu-DOTA-9A6 PET imaging. Compared with the full length antibody 9A6, the heavy chain antibody 2A3-mFc showed higher tumor uptake, lower liver uptake and shorter circulation half-life. The results from optical imaging with Cy5.5-Abs were consistent with those of PET imaging. Conclusion: The heavy chain antibody 2A3-mFc is superior to the single domain antibody and the full length antibody with regard to tumor detection and biodistribution.

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