Annexin V recognizes
apoptotic cells by specific
molecular interaction with
phosphatidyl serine, a
lipid that is normally sequestered in the inner leaflet of the
cell membrane, but is translocated to the outer leaflet in
apoptotic cells, such as
foam cells of
atherosclerotic plaque.
Annexin V could potentially deliver carried materials (such as superparamagnetic
contrast agents for
magnetic resonance imaging) to sites containing
apoptotic cells, such as high grade
atherosclerotic lesions, so we administered biochemically-derivatized (
annexin V) superparmagnetic
iron oxide particles (SPIONs)
parenterally to two related rabbit models of human
atherosclerosis. We observe development of negative
magnetic resonance imaging (
MRI) contrast in
atheromatous lesions and but not in healthy
artery. Vascular targeting by
annexin V SPIONs is atheroma-specific (i.e., does not occur in healthy control rabbits) and requires active
annexin V decorating the SPION surface. Targeted SPIONs produce negative contrast at doses that are 2,000-fold lower than reported for non-specific
atheroma uptake of untargeted superparamagnetic
nanoparticles in plaque in the same animal model. Occlusive and mural plaques are differentiable. While most of the dose accumulates in
liver,
spleen,
kidneys and
bladder,
annexin V SPIONs also partition rapidly and deeply into early
apoptotic foamy
macrophages in plaque. Contrast in plaque decays within 2 months, allowing
MRI images to be replicated with a subsequent, identical dose of
annexin V SPIONs. Thus, biologically targeted superparamagnetic
contrast agents can contribute to non-invasive evaluation of
cardiovascular lesions by simultaneously extracting morphological and biochemical data from them.
