Evaluation of α _v β ₃ Integrin-Targeted Positron Emission Tomography Tracer ¹⁸ F-Galacto-RGD for Imaging of Vascular Inflammation in Atherosclerotic Mice

Abstract

Background-18 F-Galacto-RGD is a positron emission tomography (PET) tracer binding to ␣ v ␤ 3 integrin that is expressed by macrophages and endothelial cells in atherosclerotic lesions. Therefore, we evaluated 18 F-galacto-RGD for imaging vascular inflammation by studying its uptake into atherosclerotic lesions of hypercholesterolemic mice in comparison to deoxyglucose. Methods and results-Hypercholesterolemic LDLRϪ/Ϫ ApoB 100/100 mice on a Western diet and normally fed adult C57BL/6 control mice were injected with 18 F-galacto-RGD and 3 H-deoxyglucose followed by imaging with a small animal PET/CT scanner. The aorta was dissected 2 hours after tracer injection for biodistribution studies, autoradiography, and histology. Biodistribution of 18 F-galacto-RGD was higher in the atherosclerotic than in the normal aorta. Autoradiography demonstrated focal 18 F-galacto-RGD uptake in the atherosclerotic plaques when compared with the adjacent normal vessel wall or adventitia. Plaque-to-normal vessel wall ratios were comparable to those of deoxyglucose. Although angiogenesis was not detected, 18 F-galacto-RGD uptake was associated with macrophage density and deoxyglucose accumulation in the plaques. Binding to atherosclerotic lesions was efficiently blocked in competition experiments. In vivo imaging visualized 18 F-galacto-RGD uptake colocalizing with calcified lesions of the aortic arch as seen in CT angiography. Conclusions-18 F-Galacto-RGD demonstrates specific uptake in atherosclerotic lesions of mouse aorta. In this model, its uptake was associated with macrophage density.18 F-Galacto-RGD is a potential tracer for noninvasive imaging of inflammation in atherosclerotic lesions. (Circ Cardiovasc Imaging. 2009;2:331-338.)

64Cu-Labeled Divalent Cystine Knot Peptide for Imaging Carotid Atherosclerotic Plaques

“…However, their accumulation in atherosclerotic lesions and their plaque-to-normal tissue ratios are low in preclinical models. The uptake of 18 F-galacto-RGD by the aorta plaque was only 0.24 percentage injected dose per gram (%ID/g) at 2 h after injection, and the aorta-to-normal vessel wall uptake ratio was 1.3 (13). The aorta plaque uptake of 68 Ga-DOTA-RGD was 0.90 %ID/g at 1 h after injection, and aorta-to-heart and aortato-blood uptake ratios were 1.8 and 1.1 at 1 h after injection, respectively (17).…”

“…However, 18 F-FDG is a nonspecific imaging probe for inflammation, because it can also accumulate in calcified structures of vessel walls, muscle tissues adjacent to the vessels, and tissues with high metabolic rates such as the myocardium and brain. Therefore, new PET probes to image plaque-related inflammation and their propensity to rupture are needed in treating heart disease (13).…”

“…Integrin a v b 3 receptors are transmembrane glycoproteins, which are highly expressed by not only activated endothelial cells of new vessels in the atherosclerotic plaques, but also activated macrophages that mediate the inflammatory process. Therefore, radiolabeled peptides such as Arg-Gly-Aspartic acid (RGD) peptide that specifically bind to a v b 3 integrin have been studied by PET imaging of atherosclerotic plaques (13,(17)(18)(19)(20). For example, 18 Fgalacto-RGD (13) and 68 Ga-DOTA-RGD (17) have shown specific targeting to integrin a v b 3 .…”

New Targets of Molecular Imaging in Atherosclerosis: Prehension of Current Status

“…46,47 Recently, human carotid atherosclerosis imaging was evaluated by PET/CT multimodality using the 18 F-galacto-RGD probe. 48 During atherogenesis, arterial vessels undergo fibrosis and deposit minerals in the plaque area.…”

Specificity vs versatility: A fine balance for novel targeted molecular imaging radiotracers

“…F-galacto-RGD), 5 elastin expression by vascular endothelial cells (e.g., 64 Cu-G1C glycoprotein), 6 or matrix metalloproteinase expression in extracellular matrix (e.g.,…”