Table 2.

Inflammatory molecular targets in the atherosclerotic plaque

Target	Imaging modality	Animal/human	Atherosclerosis model	In vivo imaging	Histological validation	Results
Macrophages	PET52-59,61,62	NZW rabbits	Yes	Yes	Yes	FDG uptake shows a good correlation with macrophage count FDG uptake can possibly identify non stenotic culprit plaques FDG uptake was attenuated with lipid lowering treatment
		WHHL rabbits	Yes	Yes	Yes
		Humans	Yes	Yes	Yes
	MRI63-71	ApoE−/− mice	Yes	Yes	Yes	Macrophage SPIO internalization is under influence of cytokines, serum components and statin treatment Signal decrease after SPIO administration was associated with increased endothelial permeability, high macrophage content and plaque vulnerability SPIO was able to identify fatty streaks
		WHHL rabbits	Yes	Yes	Yes
		HHL rabbits	Yes	Yes	Yes
		Humans	Yes	Yes	Yes
	CT49	NZW rabbits	Yes	Yes	Yes	Iodinated nanoparticles identified the presence of macrophages
Macrophage scavenger receptor	MRI72	ApoE−/− mice	Yes	No	Yes	Gadolinium immunomicelles targeted at the macrophage scavenger receptor are specifically internalized by macrophages
VCAM-1	Ultrasound73	ApoE−/− mice	Yes	Yes	Yes	Targeted microbubbles attached to endothelial cells under pulsatile high shear stress
	MRI76,77,87	ApoE−/− mice	Yes	Yes	Yes	Targeted SPIO compounds attached to activated endothelial cells of early atheromas Statin treatment reduced VCAM-1 binding by targeted SPIO
		Humans	Yes	No	Yes
ICAM-1	Ultrasound74,75	Yucatan swine	Yes	Yes	No	Targeted microbubbles attached to endothelial cells of early atheromas
	MRI78	SJL/J mice	No	No	Yes	Plaque MR signal increase substantially after gadolinium contrast administration
e-selectin	MRI83-85	nu/nu mice	No	Yes	Yes	Targeted SPIO significantly decreased the T2 time in the vessels wall Targeted gadolinium compounds significantly prolonged contrast retention in the plaque
		Balb/c By JICo mice	No	Yes	No
		Wistar rats	No	Yes	No
p-selectin	MRI87	ApoE−/− mice	Yes	No	Yes	Targeted SPIO showed specific attachment to endothelial cells
p-selectin and VCAM-1	MRI87	ApoE−/− mice	Yes	No	Yes	Dual-targeted SPIO bound significantly stronger than separate targeted SPIO’s
MMP	MRI89	ApoE−/− mice	Yes	Yes	Yes	MMP targeted gadolinium assisted in the differentiation between MMP-rich and MMP-poor plaques
		Humans	Yes	No	Yes
	SPECT90	ApoE−/− mice	Yes	Yes	Yes	A 99mTc-labeled MMP inhibitor identified MMP activity in vivo
		LDLR−/− mice	Yes	Yes	Yes

CT, Computed tomography; FDG, ¹⁸F-fluorodeoxyglucose; ICAM-1, intercellular adhesion molecule-1; MMP, matrix metalloproteinase; MRI, magnetic resonance imaging; PET, positron emission tomography; SPECT, single photon emission computed tomography; SPIO, super paramagnetic iron oxide compound; VCAM-1, vascular cell adhesion molecule-1.