Journal of Nuclear Cardiology

2017

DOI: 10.1007/s12350-016-0552-x

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Targeting activated macrophages to identify the vulnerable atherosclerotic plaque

Lynne L. Johnson

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Role Of Inflammatory Cytokines In the Pathogenesis Of Ath1

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Cited by 3 publications

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“…The high and specific lung uptake of TSPO radioligands has been considered as a potential limiting factor in using TSPO as an imaging target in vascular imaging [ 34 ]. The lung uptake is most likely caused by resident inflammatory cells with high TSPO expression [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Positron Emission Tomography Imaging of Macrophages in Atherosclerosis with ¹⁸F-GE-180, a Radiotracer for Translocator Protein (TSPO)

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et al. 2018

Contrast Media & Molecular Imaging

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Intraplaque inflammation plays an important role in the progression of atherosclerosis. The 18 kDa translocator protein (TSPO) expression is upregulated in activated macrophages, representing a potential target to identify inflamed atherosclerotic plaques. We preclinically evaluated 18F-GE-180, a novel third-generation TSPO radioligand, in a mouse model of atherosclerosis. Methods. Nine hypercholesterolemic mice deficient in low density lipoprotein receptor and apolipoprotein B48 (LDLR−/−ApoB100/100) and six healthy C57BL/6N mice were injected with 10 MBq of 18F-GE-180. Specificity of binding was demonstrated in three LDLR−/−ApoB100/100 mice by injection of nonradioactive reference compound of 18F-GE-180 before 18F-GE-180. Dynamic 30-minute PET was performed followed by contrast-enhanced CT, and the mice were sacrificed at 60 minutes after injection. Tissue samples were obtained for ex vivo biodistribution measurements, and aortas were cut into serial cryosections for digital autoradiography. The presence of macrophages and TSPO was studied by immunohistochemistry. The 18F-GE-180 retention in plaque areas with different macrophage densities and lesion-free vessel wall were compared. Results. The LDLR−/−ApoB100/100 mice showed large, inflamed plaques in the aorta. Autoradiography revealed significantly higher 18F-GE-180 retention in macrophage-rich plaque areas than in noninflamed areas (count densities 150 ± 45 PSL/mm2 versus 51 ± 12 PSL/mm2, p < 0.001). Prominent retention in the vessel wall without plaque was also observed (220 ± 41 PSL/mm2). Blocking with nonradioactive GE-180 diminished the difference in count densities between macrophage-rich and noninflamed areas in atherosclerotic plaques and lowered the count density in vessel wall without plaque. Conclusion. 18F-GE-180 shows specific uptake in macrophage-rich areas of atherosclerotic plaques in mice. However, retention in atherosclerotic lesions does not exceed that in lesion-free vessel wall. The third-generation TSPO radioligand 18F-GE-180 did not show improved characteristics for imaging atherosclerotic plaque inflammation compared to previously studied TSPO-targeting tracers.

“…The high and specific lung uptake of TSPO radioligands has been considered as a potential limiting factor in using TSPO as an imaging target in vascular imaging [ 34 ]. The lung uptake is most likely caused by resident inflammatory cells with high TSPO expression [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Positron Emission Tomography Imaging of Macrophages in Atherosclerosis with ¹⁸F-GE-180, a Radiotracer for Translocator Protein (TSPO)

¹

,

²

,

³

et al. 2018

Contrast Media & Molecular Imaging

View full text Add to dashboard Cite

Intraplaque inflammation plays an important role in the progression of atherosclerosis. The 18 kDa translocator protein (TSPO) expression is upregulated in activated macrophages, representing a potential target to identify inflamed atherosclerotic plaques. We preclinically evaluated 18F-GE-180, a novel third-generation TSPO radioligand, in a mouse model of atherosclerosis. Methods. Nine hypercholesterolemic mice deficient in low density lipoprotein receptor and apolipoprotein B48 (LDLR−/−ApoB100/100) and six healthy C57BL/6N mice were injected with 10 MBq of 18F-GE-180. Specificity of binding was demonstrated in three LDLR−/−ApoB100/100 mice by injection of nonradioactive reference compound of 18F-GE-180 before 18F-GE-180. Dynamic 30-minute PET was performed followed by contrast-enhanced CT, and the mice were sacrificed at 60 minutes after injection. Tissue samples were obtained for ex vivo biodistribution measurements, and aortas were cut into serial cryosections for digital autoradiography. The presence of macrophages and TSPO was studied by immunohistochemistry. The 18F-GE-180 retention in plaque areas with different macrophage densities and lesion-free vessel wall were compared. Results. The LDLR−/−ApoB100/100 mice showed large, inflamed plaques in the aorta. Autoradiography revealed significantly higher 18F-GE-180 retention in macrophage-rich plaque areas than in noninflamed areas (count densities 150 ± 45 PSL/mm2 versus 51 ± 12 PSL/mm2, p < 0.001). Prominent retention in the vessel wall without plaque was also observed (220 ± 41 PSL/mm2). Blocking with nonradioactive GE-180 diminished the difference in count densities between macrophage-rich and noninflamed areas in atherosclerotic plaques and lowered the count density in vessel wall without plaque. Conclusion. 18F-GE-180 shows specific uptake in macrophage-rich areas of atherosclerotic plaques in mice. However, retention in atherosclerotic lesions does not exceed that in lesion-free vessel wall. The third-generation TSPO radioligand 18F-GE-180 did not show improved characteristics for imaging atherosclerotic plaque inflammation compared to previously studied TSPO-targeting tracers.

“…The expression and/or activities of MMPs and TIMPs are adjusted by cytokines [ 18 ]. Vulnerable plaques have very few SMCs and high macrophage substance and are susceptible to rupture leading to thrombosis in the end [ 19 ]. What is more, key components involved in thrombosis are also the target of regulation by cytokines [ 20 ].…”

Section: Role Of Inflammatory Cytokines In the Pathogenesis Of Athmentioning

confidence: 99%

Traditional Chinese Medicine Protects against Cytokine Production as the Potential Immunosuppressive Agents in Atherosclerosis

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et al. 2017

Journal of Immunology Research

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Atherosclerosis is a chronic inflammatory disease caused by dyslipidemia and mediated by both innate and adaptive immune responses. Inflammation is a critical factor at all stages of atherosclerosis progression. Proinflammatory cytokines accelerate atherosclerosis progression, while anti-inflammatory cytokines ameliorate the disease. Accordingly, strategies to inhibit immune activation and impede immune responses towards anti-inflammatory activity are an alternative therapeutic strategy to conventional chemotherapy on cardiocerebrovascular outcomes. Since a number of Chinese medicinal plants have been used traditionally to prevent and treat atherosclerosis, it is reasonable to assume that the plants used for such disease may suppress the immune responses and the resultant inflammation. This review focuses on plants that have immunomodulatory effects on the production of inflammatory cytokine burst and are used in Chinese traditional medicine for the prevention and therapy of atherosclerosis.

Review of cardiovascular imaging in the Journal of Nuclear Cardiology 2017. Part 1 of 2: Positron emission tomography, computed tomography, and magnetic resonance

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2018

Journal of Nuclear Cardiology

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Several original articles and editorials have been published in the Journal of Nuclear Cardiology in 2017. It has become a tradition at the beginning of each year to summarize some of these key articles in 2 sister reviews. In this first part one, we will discuss some of the progress made in the field of heart failure (cardio-oncology, myocardial blood flow, viability, dyssynchrony, and risk stratification), inflammation, molecular and hybrid imaging using advancement in positron emission tomography, computed tomography, and magnetic resonance imaging.

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