Radionuclide Imaging for the Detection of Inflammation in Vulnerable Plaques
John R. Davies, BSc, MBBS, MRCP*,
James H.F. Rudd, PhD, MRCP ,
Peter L. Weissberg, MD, FRCP*,* and
Jagat Narula, MD, PhD, FACC
* Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom
Imaging Science Laboratory, Mount Sinai Hospital, New York, New York
University of California-Irvine School of Medicine, Irvine, California
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Figure 1 Targets for nuclear imaging of plaque inflammation. Schematic representation of inflammatory cells, molecules, and processes that present potential targets for the identification of vulnerable plaques. CCR-2 = chemokine receptor 2; CD36; cluster differentiation 36; GLUT = glucose uptake transporter; IEL = internal elastic lamina; MCP-1 = monocyte chemotactic protein-1; MMP = matrix metalloproteinase; oxLDL = oxidized low-density lipoprotein; PS = phosphatidyl serine; SR-A = scavenger receptor-A.
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Figure 2 In vivo gamma camera images of experimental aortic atheroma after injection of 99mtechnetium-malondialdehyde-2 (Tc-MDA2). En-face preparations of Sudan-stained aortas from an apolipoprotein E null (ApoE–/–) mouse (A) and a Watanabe heritable hyperlipidemic (WHHL) rabbit (B) injected with 125I-MDA2, a murine antibody binding to malondialdehyde–low-density lipoprotein, a model oxLDL epitope. Red color (left panels in A and B) represents plaque stained with Sudan IV, and black color (right panels in A and B) in the corresponding autoradiograph represents accumulated 125I-MDA2 reflecting the presence of oxLDL. (C) shows the relationship of 125I-MDA2 uptake and plaque burden as measured by aortic weight. (D and E) represent in vivo imaging of atherosclerotic WHHL (D) and non-atherosclerotic New Zealand White (E) rabbits with 99mTc-MDA2. Abbreviations as in Figure 1. Reprinted, with permission, from Tsimikas et al. (13).
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Figure 3 In vivo single-photon emission computed tomography imaging and quantification of matrix metalloproteinase activity in experimental carotid lesions with the tracer, 123I-HO-CGS 27023A. Representative planar images taken 10 min (left) and 120 min (right) after injection in (A to C) apolipoprotein E-deficient (ApoE–/–) mice and (D) wild-type (WT) mice 4 weeks after carotid ligation. (A) Unblocked; (B) after pre-dosing with 6 mmol/l CGS27023A; (C) sham-operated; (D) WT; (E) quantitative uptake of the radioligand in the carotid lesion; and (F) tissue uptake over time expressed as % injected dose. *p < 0.05 between unblocked and pre-dosed lesional uptake. The signal in the abdominal cavity is non-specific and probably reflects metabolism of the original compound, because there is no inhibition after pre-dosing in all experiments. Reprinted, with permission, from Schafers et al. (21).
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Figure 4 Single-photon emission computed tomography (SPECT) images of unstable atherosclerotic carotid artery lesions obtained with Tc99m-annexin-A5. (A) shows transverse and coronal views obtained by SPECT in Patient #1, who had a left-sided transient ischemic attack (TIA) 3 days before imaging. Patient #1 had significant stenoses of both carotid arteries; however, the uptake of Tc99m-annexin-A5 is evident only in the culprit lesion (arrows). Histopathology of an endarterectomy specimen from Patient #1 (B, anti–annexin-A5 antibody) shows substantial infiltration of macrophages into the neointima, with extensive binding of annexin-A5 (brown staining). In contrast, SPECT images of Patient #2 (C), who had had a right-sided TIA three months before imaging, do not show annexin-A5 uptake in the carotid region on both sides. Doppler ultrasonography revealed a clinically significant obstructive lesion on the affected side. Histopathological analysis of an endarterectomy specimen from Patient #2 (D) shows a lesion rich in smooth-muscle cells, with negligible binding of annexin-A5. ANT = anterior; L = left. Reprinted, with permission, from Kietselaer et al. (25).
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Figure 5 Positron emission tomography (PET) images from patients with unstable carotid disease after administration of fluorine-18–labeled deoxyglucose (FDG). (A) FDG-PET (left column), computed tomography (CT) angiography (middle column), and fused (right column) images from patient with symptomatic carotid stenosis (top row) and contralateral asymptomatic carotid stenosis (bottom row). The yellow arrows highlight areas of FDG uptake corresponding to stenotic carotid plaque. (B) A graph showing FDG accumulation rate in symptomatic versus asymptomatic carotid plaques. Note that FDG uptake into symptomatic plaque was significantly higher. Modified, with permission, from original figure by Rudd et al. (39).
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Figure 6 Images obtained by combined positron emission tomography (PET)/computed tomography (CT) machine after administration of fluorine-18–labeled deoxyglucose (FDG) in patients with aortic atheroma. Top row: coronal CT (left), FDG-PET (middle), and fused (right) images. There is no calcium present in the aortic wall on CT. On the PET and fused images grade 1 (arrows) and grade 3 (arrowheads), FDG uptake can be seen in the aortic wall. Bottom row: transaxial CT (left), FDG-PET (middle), and fused (right) images. The CT image shows marked calcification present on the medial side of the descending aorta (arrow), which on the FDG-PET and fused images demonstrates grade 1 FDG uptake (arrows) indicating mild inflammation. Grade 3 FDG uptake is also seen on the lateral side of descending aorta (arrowheads) indicating a higher level of inflammation in this segment of non-calcified vessel wall. Modified, with permission, from Tatsumi et al. (42).
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Figure 7 Images from combined positron emission tomography (PET)/computed tomography (CT) scanner showing coronary fluorine-18–labeled deoxyglucose (FDG) uptake. Fused PET/CT images show contiguous transaxial slices through heart. Inflammation (arrowheads) is present proximal and distal to the calcified left anterior descending artery (arrow). A tumor sits adjacent to esophagus. Reprinted, with permission, from Dunphy et al. (43).
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