Molecular Imaging of Endothelial Adhesion Molecules - Adhesion Molecules - page 59

(2007) have developed a novel, targeted microparticle of iron oxide (MPIO) probe
that can identify VCAM-1 expression in vivo in mouse acute brain inl ammation.
MPIO (1 μm diameter), with reactive tosyl groups, were used for direct covalent
conjugation of monoclonal VCAM-1 antibodies (VCAM-MPIO). h e capacity of
VCAM-MPIO for specii c binding was i rst demonstrated in vitro using activated
mouse endothelial cells (sEND-1) stimulated with graded doses of tumor necrosis
factor alpha (TNF-α). h e ability of VCAM-MPIO to demonstrate endothelial
inl ammation using in vivo mMRI was then tested in a mouse model of acute
brain inl ammation. Acute inl ammation was induced by stereotactic injection of
the proinl ammatory interleukin 1β (IL-1β) into the let corpus striatum, while
the right hemisphere received no injection and served as an internal control. At er
3 hr, VCAM-MPIO or negative isotype control IgG-MPIO (4 × 10 8 MPIO) were
intravenously injected via a tail vein and allowed to circulate for 1.5-2 hr prior to
MRI. VCAM-MPIO generated highly specii c, potent hypo-intense contrast ef ects
in the IL-1β-activated hemisphere, which delineated the architecture of activated
cerebral blood vessels, with minimal background contrast (Fig. 2) . h e specii city
and potency of the contrast ef ects derived from a combination of targeted delivery
of a large amount of iron oxide to sites of early inl ammation and rapid clearance
of MPIO from the blood, which minimized background signal.
Fig. 2 Targeted microparticle of iron oxide detection using MRI. In vivo T2*-weighted coronal
images from 3D gradient echo data sets of a mouse brain with ~90 μm isotropic resolution. Four
slices are shown per brain. Top row: Mouse injected intrastriatally with 1 ng of IL-1β in 1 μl of
saline 3 hr prior to IV injection of VCAM-MPIO. Areas of low signal (black) in the let hemisphere
rel ect MPIO retention on acutely inl amed endothelium. h e opposite hemisphere shows almost
no signal dropout. Bot om row: Identical experiment but using IgG-MPIO as a control. No signal
dropout is seen in the inl amed hemisphere. With permission from McAteer et al. (2007).
Dual-ligand MPIO (4.5 μm diameter) was subsequently designed to mimic
more closely leukocyte binding pathways in vivo ; since in vivo leukocyte binding