Molecular targeting of CEACAM6 using antibody probes of different sizes.

Journal of Controlled Release : Official Journal of the Controlled Release Society
Gang NiuXiaoyuan Chen

Abstract

Carcinocinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is overexpressed in a number of human malignancies, especially in pancreatic cancer. It has been demonstrated that CEACAM6 is a potential target for monoclonal antibody (mAb) therapy with a safe therapeutic index. Here, we labeled three anti-CEACAM6 antibodies of different sizes, including a single-domain antibody 2A3 (16 kDa), a heavy chain antibody 2A3-mFc (80 kDa) and a full length antibody 9A6 (150 kDa), with ⁶⁴Cu to image CEACAM6 expression in a xenografted pancreatic tumor model. For positron emission tomography (PET) imaging, the tumor mice were intravenously injected with ⁶⁴Cu-DOTA-antibodies and static scans were obtained at 5 min, 0.5, 1, 2, 4, 8 and 24h post-injection (p.i.). All three antibodies showed strong CEACAM6 binding. Ex vivo immunostaining on tumor sections at 24 h after Ab injection demonstrated specific tumor targeting of both 2A3-mFc and 9A6. ⁶⁴Cu-DOTA-2A3 showed fast BxPC3 tumor uptake and rapid whole-body clearance. At 24 h p.i., the tumor uptakes were 98.2±6.12%ID/g for ⁶⁴Cu-DOTA-2A3-mFc and 57.8±3.73%ID/g for ⁶⁴Cu-DOTA-9A6, respectively. Compared with the full length antibody 9A6, the heavy chain antibody 2A3-mFc showed higher tu...Continue Reading

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Citations

Dec 2, 2015·Molecular Pharmaceutics·Christopher G EnglandWeibo Cai
Nov 28, 2014·Virchows Archiv : an International Journal of Pathology·Ok-Jun LeeHyung Geun Song
Apr 29, 2016·Journal of Labelled Compounds & Radiopharmaceuticals·Chongjiao LiXiaoli Lan
Nov 21, 2018·The Biochemical Journal·Martin A RossottiC Roger MacKenzie
Feb 11, 2014·Current Protocols in Immunology·Toya Nath BaralMehdi Arbabi Ghahroudi
Apr 4, 2021·Journal of Clinical Medicine·Ruth González-GómezAlberto J Schuhmacher

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