Recent Advances in the Development of PET/SPECT Probes for Atherosclerosis Imaging

Shimizu, Yoichi; Kuge, Yuji

doi:10.1007/s13139-016-0418-9

Cited by 8 publications

(3 citation statements)

References 62 publications

(52 reference statements)

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“…Normal arterial endothelial cells have biological functions of barrier effect, anticoagulation, regulation of vascular tension, and activation of inflammatory mediators [ 16 ]. In the process of AS, vascular endothelial cells are impaired by chronic inflammation.…”

Section: Discussionmentioning

confidence: 99%

miRNA-576 Alleviates the Malignant Progression of Atherosclerosis through Downregulating KLF5

et al. 2021

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Objective. To elucidate the role of microRNA-576 (miRNA-576) in alleviating the deterioration of atherosclerosis (AS) through downregulating krüpple-like factor 5 (KLF5). Materials and Methods. The AS model in mice was first constructed. Body weight, inflammation degrees, blood lipid, and relative levels of KLF5, miRNA-576, caspase-3, and bcl-2 in AS mice and control mice were compared. Dual-luciferase reporter gene assay was performed to evaluate the binding between miRNA-576 and KLF5. RAW264.7 cells were treated with 200 mg/L ox-LDL for establishing in vitro high-fat model. Regulatory effects of miRNA-576/KLF5 on relative levels of β-catenin and inflammatory factors in RAW264.7 cells were explored. Results. Body weight was heavier in AS mice than in controls. Protein levels of KLF5 and caspase-3 were upregulated, while bcl-2 was downregulated in AS mice. In particular, protein level of KLF5 was highly expressed in aortic tissues of AS mice. TC and LDL increased, and HDL decreased in AS mice compared with controls. Inflammatory factor levels were markedly elevated in AS mice. KLF5 was verified to be the target gene binding miRNA-576. Overexpression of miRNA-576 downregulated KLF5, inflammatory factors, and β-catenin in ox-LDL-treated RAW264.7 cells. Regulatory effect of miRNA-576 on the release of inflammatory factors in RAW264.7 cells could be partially abolished by KLF5. Conclusions. miRNA-576 alleviates malignant progression of AS via downregulating KLF5.

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Section: Discussionmentioning

confidence: 99%

miRNA-576 Alleviates the Malignant Progression of Atherosclerosis through Downregulating KLF5

et al. 2021

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“…This modality uses a blend of radioactive tracers, such as 99m Tc, iodine-123 ( 123 I), and Indium-111 ( 111 In)eemitting gamma rays, and probes specific for cells to create an image. 35,36 Although SPECT imaging may not provide the same spatiotemporal resolution as MRI or PET, it does offer a myriad of other advantages, including being more accessible to bedside imaging of patients, less expensive, and using radionucleotides that decay at a slower rate, which permits longer time for study. 37,38 In addition, SPECT provides a comprehensive threedimensional representative image of aneurysm formation.…”

Section: Discussionmentioning

confidence: 99%

Single-Photon Emission Computed Tomography Imaging Using Formyl Peptide Receptor 1 Ligand Can Diagnose Aortic Aneurysms in a Mouse Model

Shannon

Chordia

Spinosa

et al. 2020

Journal of Surgical Research

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Background: Our previous studies showed that neutrophil infiltration and activation plays an important role in the pathogenesis of abdominal aortic aneurysms (AAA). However, there is a lack of noninvasive, inflammatory cell-specific molecular imaging methods to provide early diagnosis of AAA formation. Formyl peptide receptor 1 (FPR1) is rapidly upregulated on neutrophils during inflammation. Therefore, it is hypothesized that the use of cinnamoyl-F-(D)L-F-(D)L-F-K (cFLFLF), a PEGylated peptide ligand that binds FPR1 on activated neutrophils, would permit accurate and noninvasive diagnosis of AAA via singlephoton emission computed tomography (SPECT) imaging.Materials and methods: Male C57BL/6 (wild-type) mice were treated with topical elastase (0.4 U/mL type 1 porcine pancreatic elastase) or heat-inactivated elastase (control), and aortic diameter was measured by video micrometry. Comparative histology was performed on Day 14 to assess neutrophil infiltration in aortic tissue. We performed near-infrared fluorescence imaging using c-FLFLF-Cy7 probe on Days 7 and 14 postelastase treatment and measured fluorescence intensity ex vivo in excised aortic tissue. A separate group of animals were injected with 99m Tc-c-FLFLF 2 h before SPECT imaging on Day 14 using a SPECT/computed tomography/positron emission tomography trimodal scanner. Coexpression of neutrophils with c-FLFLF was also performed on aortic tissue by immunostaining on Day 14.Results: Aortic diameter was significantly increased in the elastase group compared with controls on Days 7 and 14. Simultaneously, a marked increase in neutrophil infiltration and elastin degradation as well as decrease in smooth muscle integrity were observed in aortic tissue after elastase treatment compared with controls. Moreover, a significant increase in fluorescence intensity of c-FLFLF-Cy7 imaging probe was also observed in elastase-treated mice on Day 7 (approximately twofold increase) and Day 14 (approximately 2.5-fold increase) compared with respective controls. SPECT imaging demonstrated

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“…One strategy to solve this problem is to connect two Ham groups with a propylene linker, which was reported to reduce liver retention in a previous report [24]. Regarding the diagnosis of atherosclerosis, some previously reported probes also had high accumulation in the liver [25]. Therefore, [ 99m Tc]Tc-BOD holds potential for imaging lipid droplets in atherosclerotic lesions.…”

Section: Discussionmentioning

confidence: 99%

Development of Technetium-99m-Labeled BODIPY-Based Probes Targeting Lipid Droplets Toward the Diagnosis of Hyperlipidemia-Related Diseases

et al. 2019

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Hyperlipidemia causes systemic lipid disorder, which leads to hepatic steatosis and atherosclerosis. Thus, it is necessary to detect these syndromes early and precisely to improve prognosis. In the affected regions, abnormal formation and growth of lipid droplets is observed; therefore, lipid droplets may be a suitable target for the diagnosis of hyperlipidemia-related syndromes. In this study, we designed and synthesized [99mTc]Tc-BOD and [99mTc]Tc-MBOD composed of one technetium-99m and two BODIPY scaffolds with hydroxamamide (Ham) or N-methylated hydroxamamide (MHam) in radiochemical yields of 54 and 35%, respectively, with a radiochemical purity of over 95%. [99mTc]Tc-BOD showed significantly higher accumulation levels in foam cells than in non-foam cells (foam cells: 213.8 ± 64.8, non-foam cell: 126.2 ± 26.9 %dose/mg protein, p < 0.05) 2 h after incubation. In contrast, [99mTc]Tc-MBOD showed similar accumulation levels in foam cells and non-foam cells (foam cells: 92.2 ± 23.3, non-foam cell: 83.8 ± 19.8 %dose/mg protein). In normal mice, [99mTc]Tc-BOD exhibited gradual blood clearance (0.5 h: 4.98 ± 0.35, 6 h: 1.94 ± 0.12 %ID/g) and relatively high accumulation in the liver 6 h after administration (15.22 ± 1.72 %ID/g). Therefore, [99mTc]Tc-BOD may have potential as an imaging probe for detecting lipid droplets in disease lesions of hyperlipidemia.

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Recent Advances in the Development of PET/SPECT Probes for Atherosclerosis Imaging

Cited by 8 publications

References 62 publications

miRNA-576 Alleviates the Malignant Progression of Atherosclerosis through Downregulating KLF5

miRNA-576 Alleviates the Malignant Progression of Atherosclerosis through Downregulating KLF5

Single-Photon Emission Computed Tomography Imaging Using Formyl Peptide Receptor 1 Ligand Can Diagnose Aortic Aneurysms in a Mouse Model

Development of Technetium-99m-Labeled BODIPY-Based Probes Targeting Lipid Droplets Toward the Diagnosis of Hyperlipidemia-Related Diseases

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