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Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography.

ABSTRACT: Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using (18)F-sodium fluoride ((18)F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of (18)F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse (18)F-NaF binding. We show that (18)F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. (18)F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of (18)F-NaF may foster new approaches to developing treatments for vascular calcification.

SUBMITTER: Irkle A

PROVIDER: S-EPMC4506997 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography.

Irkle Agnese A Vesey Alex T AT Lewis David Y DY Skepper Jeremy N JN Bird Joseph L E JL Dweck Marc R MR Joshi Francis R FR Gallagher Ferdia A FA Warburton Elizabeth A EA Bennett Martin R MR Brindle Kevin M KM Newby David E DE Rudd James H JH Davenport Anthony P AP

Nature communications 20150707

Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using (18)F-sodium fluoride ((18)F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise ...[more]

PMID: 26151378

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Project description:BackgroundAs a noninvasive diagnostic tool, fluorine-18-labelled sodium fluoride positron emission tomography ([18F]NaF PET) has been increasingly applied in clinical practice due to its excellent imaging performance, attracting more attention from clinical practitioners. However, with the continuous development of technology and growth of knowledge, the field of [18F]NaF PET is changing. Nevertheless, few studies have conducted quantitative analyses of the literature in this field. Therefore, in this study, we used bibliometric methods to analyze the trends, content distribution, and frontiers of this field from multiple perspectives, including social and international structure, conceptual structure, and intellectual structure.MethodsThis study used the Web of Science (WOS) core database as the data source and retrieved literature related to [18F]NaF PET between 2008 and 2022. CiteSpace and VOSviewer software were then employed for bibliometric analysis. This study performed co-occurrence analysis and citation analysis to investigate the characteristics of [18F]NaF PET in 3 aspects.ResultsA total of 682 articles related to [18F]NaF PET were collected during the period from 2008 to 2022. The author, Alavi, had the highest number of publications (67 articles). In terms of institutions, the University of Edinburgh had the highest number of publications (64 articles). The United States (300 articles) was the country with the highest number of published articles. Keyword co-occurrence analysis revealed that [18F]NaF PET-related technologies, bone metastasis (prostate cancer and breast cancer), and atherosclerosis were prominent research directions in this field. In terms of highly cited authors, Even-Sapir had the highest citation count (188 citations). Regarding highly cited journals, the Journal of Nuclear Medicine ranked as the most highly cited journal. The literature co-citation clustering and timeline graph showed that atherosclerotic plaques, bone metastasis, and the clinical applications of [18F]NaF PET were topics of active research in this field.ConclusionsThere has been an increase in the literature published in the field of [18F]NaF PET from 2008 to 2022. The United States holds a prominent position in the field of [18F]NaF PET. Arteriosclerosis and bone metastasis are the main topics in this field and at the forefront of research.

Project description:18F-sodium fluoride (18F-NaF) is a positron emission tomography (PET) radiotracer widely used in skeletal imaging and has also been proposed as a biomarker of active calcification in atherosclerosis. Like most PET radiotracers, 18F-NaF is typically administered intravenously. However in small animal research intravenous administrations can be challenging, because partial paravenous injection is common due to the small calibre of the superficial tail veins and repeat administrations via tail veins can lead to tissue injury therefore limiting the total number of longitudinal scanning points. In this paper, the feasibility of using intra-peritoneal route of injection of 8F-NaF to study calcification in mice was studied by looking at the kinetic and uptake profiles of normal soft tissues and bones versus intra-vascular injections. Dynamic PET was performed for 60 min on nineteen isoflurane-anesthetized male Swiss mice after femoral artery (n = 7), femoral vein (n = 6) or intraperitoneal (n = 6) injection of 8F-NaF. PET data were reconstructed and the standardised uptake value (SUV) and standardised uptake value ratio (SUVr) were estimated from the last three frames between 45- and 60-min and 8F-NaF uptake constant (Ki) was derived by Patlak graphical analysis. In soft tissue, the 18F-NaF perfusion phase changes depending on the type on injection route, whereas the uptake phase is similar regardless of the administration route. In bone tissue SUV, SUVr and Ki measures were not significantly different between the three administration routes. Comparison between PET and CT measures showed that bones that had the highest CT density displayed the lowest PET activity and conversely, bones where CT units were low had high 8F-NaF uptake. Intraperitoneal injection is a valid and practical alternative to the intra-vascular injections in small-animal 18F-NaF PET imaging providing equivalent pharmacokinetic data. CT outcome measures report on sites of stablished calcification whereas PET measures sites of higher complexity and active calcification.

Dataset Information

Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography.

Publications

Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography.

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