Development of an Anti-Vascular Cell Adhesion Protein-1 Aptamer for Molecular Imaging and Inflammation Detection in Transgenic Mouse Model of Alzheimer's Disease.
Cerebrovascular inflammation is often involved in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Non-invasive and sensitive molecular imaging of cerebrovascular inflammation biomarkers therefore represents a potential AD diagnostic and therapeutic monitoring method. Here, we describe the development of a novel aptamer-based near infrared fluorescence imaging probe targeting Vascular Cell Adhesion Molecule-1 (VCAM-1), an adhesion molecule overexpressed by the activated cerebrovasculature during inflammation. A SELEX-type screening of a random ssDNA library against human VCAM-1 identified a high-affinity ssDNA aptamer with a dissociation constant of 49 nM. We demonstrated that the Cy5.5-labeled aptamer binds to activated endothelial cells, with no affinity to non-activated cells. A scrambled aptamer labeled with Cy5.5 did not image activated and non-activated endothelial cells, confirming the sequence specificity of the targeting. In vivo, the aptameric imaging agent targeting VCAM-1 successfully identified inflammation associated with amyloid-β plaques deposition in the vessels of the cerebellum of transgenic AD mice. It exhibited excellent retention by remaining bound to vessels 4 hours post-injection, indicating its effectiveness in in vivo imaging and its potential in early detection of cerebrovascular inflammation.
Teresa
T
Simao
Andy
A
Ng
Dorothy
D
Fatehi
Slavisa
S
Corluka
Abedelnasser
A
Abulrob
Mohammed
M
Zourob
D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis*; D000818:Animals; D052157:Aptamers, Nucleotide / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D004195:Disease Models, Animal; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000150:complications; D051379:Mice; D008822:Mice, Transgenic; D057054:Molecular Imaging / Q000379:methods*; D061848:Optical Imaging; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D052157:Aptamers, Nucleotide; D019010:Vascular Cell Adhesion Molecule-1