Molecular targeting of CEACAM6 using antibody probes of different sizes

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DOIResolve DOI: http://doi.org/10.1016/j.jconrel.2012.04.043
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TypeArticle
Journal titleJournal of Controlled Release
Volume161
Issue1
Pages1824; # of pages: 7
SubjectCEACAM6; pancreatic cancer; heavy chain antibody; 64Cu; positron emission tomography (PET)
AbstractCarcinocinoembryonic 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 24 h 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 tumor uptake, lower liver uptake and shorter circulation half-life. All the data supported that the heavy chain antibody 2A3-mFc is superior to the single domain antibody and the full-length antibody with regard to tumor detection and pharmacokinetics, which has great potential to be developed for CEACAM6-targeted pancreatic cancer imaging and therapy.
Publication date
PublisherElsevier
LanguageEnglish
AffiliationHuman Health Therapeutics; NRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedYes
NRC number53173
NPARC number21268236
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Record identifiera8516045-e8d1-4a05-b611-43c7773487af
Record created2013-06-07
Record modified2016-05-09
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