Vascular uptake on 18F-sodium fluoride positron emission tomography: precursor of vascular calcification?
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ABSTRACT: Background
Microcalcifications cannot be identified with the present resolution of CT; however, 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) imaging has been proposed for non-invasive identification of microcalcification. The primary objective of this study was to assess whether 18F-NaF activity can assess the presence and predict the progression of CT detectable vascular calcification.Methods and results
The data of two longitudinal studies in which patients received a 18F-NaF PET-CT at baseline and after 6 months or 1-year follow-up were used. The target to background ratio (TBR) was measured on PET at baseline and CT calcification was quantified in the femoral arteries at baseline and follow-up. 128 patients were included. A higher TBR at baseline was associated with higher calcification mass at baseline and calcification progression (β = 1.006 [1.005-1.007] and β = 1.002 [1.002-1.003] in the studies with 6 months and 1-year follow-up, respectively). In areas without calcification at baseline and where calcification developed at follow-up, the TBR was .11-.13 (P < .001) higher compared to areas where no calcification developed.Conclusion
The activity of 18F-NaF is related to the amount of calcification and calcification progression. In areas where calcification formation occurred, the TBR was slightly but significantly higher.
SUBMITTER: den Harder AM
PROVIDER: S-EPMC8648691 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC6338233 | biostudies-literature
Project description: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.
| S-EPMC4506997 | biostudies-literature
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.
| S-EPMC10585531 | biostudies-literature
Project description:Background Positron emission tomography (PET) using 18F-sodium fluoride (18F-fluoride) to detect microcalcification may provide insight into disease activity in coronary atherosclerosis. This study aimed to investigate the relationship between 18F-fluoride uptake and progression of coronary calcification in patients with clinically stable coronary artery disease. Methods Patients with established multivessel coronary atherosclerosis underwent 18F-fluoride PET-computed tomography angiography and computed tomography calcium scoring, with repeat computed tomography angiography and calcium scoring at one year. Coronary PET uptake was analyzed qualitatively and semiquantitatively in diseased vessels by measuring maximum tissue-to-background ratio. Coronary calcification was quantified by measuring calcium score, mass, and volume. Results In a total of 183 participants (median age 66 years, 80% male), 116 (63%) patients had increased 18F-fluoride uptake in at least one vessel. Individuals with increased 18F-fluoride uptake demonstrated more rapid progression of calcification compared with those without uptake (change in calcium score, 97 [39-166] versus 35 [7-93] AU; P<0.0001). Indeed, the calcium score only increased in coronary segments with 18F-fluoride uptake (from 95 [30-209] to 148 [61-289] AU; P<0.001) and remained unchanged in segments without 18F-fluoride uptake (from 46 [16-113] to 49 [20-115] AU; P=0.329). Baseline coronary 18F-fluoride maximum tissue-to-background ratio correlated with 1-year change in calcium score, calcium volume, and calcium mass (Spearman ρ=0.37, 0.38, and 0.46, respectively; P<0.0001 for all). At the segmental level, baseline 18F-fluoride activity was an independent predictor of calcium score at 12 months (P<0.001). However, at the patient level, this was not independent of age, sex, and baseline calcium score (P=0.50). Conclusions Coronary 18F-fluoride uptake identifies both patients and individual coronary segments with more rapid progression of coronary calcification, providing important insights into disease activity within the coronary circulation. At the individual patient level, total calcium score remains an important marker of disease burden and progression. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02110303.
| S-EPMC7771641 | biostudies-literature
Project description:PurposeCalcification is a hallmark of chronic tuberculosis (TB) in humans, often noted years to decades (after the initial infection) on chest radiography, but not visualized well with traditional positron emission tomography (PET). We hypothesized that sodium [(18)F]fluoride (Na[(18)F]F) PET could be used to detect microcalcifications in a chronically Mycobacterium tuberculosis-infected murine model.ProceduresC3HeB/FeJ mice, which develop necrotic and hypoxic TB lesions, were aerosol-infected with M. tuberculosis and imaged with Na[(18)F]F PET.ResultsPulmonary TB lesions from chronically infected mice demonstrated significantly higher Na[(18)F]F uptake compared with acutely infected or uninfected animals (P < 0.01), while no differences were noted in the blood or bone compartments (P > 0.08). Ex vivo biodistribution studies confirmed the imaging findings, and tissue histology demonstrated microcalcifications in TB lesions from chronically infected mice, which has not been demonstrated previously in a murine model.ConclusionNa[(18)F]F PET can be used for the detection of chronic TB lesions and could prove to be a useful noninvasive biomarker for TB studies.
| S-EPMC4561601 | biostudies-literature
Project description:Background18F-Fluoride uptake denotes calcification activity in aortic stenosis and atherosclerosis. While PET/MR has several advantages over PET/CT, attenuation correction of PET/MR data is challenging, limiting cardiovascular application. We compared PET/MR and PET/CT assessments of 18F-fluoride uptake in the aortic valve and coronary arteries.Methods and results18 patients with aortic stenosis or recent myocardial infarction underwent 18F-fluoride PET/CT followed immediately by PET/MR. Valve and coronary 18F-fluoride uptake were evaluated independently. Both standard (Dixon) and novel radial GRE) MR attenuation correction (AC) maps were validated against PET/CT with results expressed as tissue-to-background ratios (TBRs). Visually, aortic valve 18F-fluoride uptake was similar on PET/CT and PET/MR. TBRMAX values were comparable with radial GRE AC (PET/CT 1.55±0.33 vs. PET/MR 1.58 ± 0.34, P = 0.66; 95% limits of agreement - 27% to + 25%) but performed less well with Dixon AC (1.38 ± 0.44, P = 0.06; bias (-)14%; 95% limits of agreement - 25% to + 53%). In native coronaries, 18F-fluoride uptake was similar on PET/MR to PET/CT regardless of AC approach. PET/MR identified 28/29 plaques identified on PET/CT; however, stents caused artifact on PET/MR making assessment of 18F-fluoride uptake challenging.ConclusionCardiovascular PET/MR demonstrates good visual and quantitative agreement with PET/CT. However, PET/MR is hampered by stent-related artifacts currently limiting clinical application.
| S-EPMC8616877 | biostudies-literature
Project description:Background Application of 18F-sodium fluoride (18F-NaF) positron emission tomography ( PET ) to coronary artery disease has attracted interest. We investigated the utility of 18F-NaF uptake for predicting coronary events and evaluated the combined use of coronary computed tomography (CT) angiography ( CCTA ) and 18F-NaF PET /CT in coronary artery disease risk assessment. Methods and Results This study included patients with ≥1 coronary atherosclerotic lesion detected on CCTA who underwent 18F-NaF PET / CT . High-risk plaque on CCTA was defined as plaque with low density (<30 Hounsfield units) and high remodeling index (>1.1). Focal 18F-NaF uptake in each lesion was quantified using the maximum tissue:background ratio ( TBR max), and maximum TBR max per patient (M- TBR max) was determined. Thirty-two patients having a total of 112 analyzed lesions were followed for 2 years after 18F-NaF PET / CT scan, and 11 experienced coronary events (acute coronary syndrome and/or late coronary revascularization [after 3 months]). Patients with coronary events had higher M- TBR max than those without (1.39±0.18 versus 1.19±0.17, respectively; P=0.0034). The optimal M- TBR max cutoff to predict coronary events was 1.28 (area under curve: 0.79). Patients with M- TBR max ≥1.28 had a higher risk of earlier coronary events than those with lower M- TBR max ( P=0.0062 by log-rank test). In patient-based (n=41) and lesion-based (n=143) analyses of CCTA findings that predicted higher coronary 18F-NaF uptake, the presence of high-risk plaque was a significant predictor of both M- TBR max ≥1.28 and TBR max ≥1.28. Conclusions 18F-NaF PET / CT has the potential to detect high-risk coronary artery disease and individual coronary lesions and to predict future coronary events when combined with CCTA . Clinical Trial Registration URL : www.umin.ac.jp . Unique identifier: UMIN 000013735.
| S-EPMC6474946 | biostudies-literature
Project description:BackgroundFluorine-18-sodium fluoride (18F-NaF) uptake is a marker of active vascular calcification associated with high-risk atherosclerotic plaque.ObjectivesIn patients with abdominal aortic aneurysm (AAA), the authors assessed whether 18F-NaF positron emission tomography (PET) and computed tomography (CT) predicts AAA growth and clinical outcomes.MethodsIn prospective case-control (n = 20 per group) and longitudinal cohort (n = 72) studies, patients with AAA (aortic diameter >40 mm) and control subjects (aortic diameter <30 mm) underwent abdominal ultrasound, 18F-NaF PET-CT, CT angiography, and calcium scoring. Clinical endpoints were aneurysm expansion and the composite of AAA repair or rupture.ResultsFluorine-18-NaF uptake was increased in AAA compared with nonaneurysmal regions within the same aorta (p = 0.004) and aortas of control subjects (p = 0.023). Histology and micro-PET-CT demonstrated that 18F-NaF uptake localized to areas of aneurysm disease and active calcification. In 72 patients within the longitudinal cohort study (mean age 73 ± 7 years, 85% men, baseline aneurysm diameter 48.8 ± 7.7 mm), there were 19 aneurysm repairs (26.4%) and 3 ruptures (4.2%) after 510 ± 196 days. Aneurysms in the highest tertile of 18F-NaF uptake expanded 2.5× more rapidly than those in the lowest tertile (3.10 [interquartile range (IQR): 2.34 to 5.92 mm/year] vs. 1.24 [IQR: 0.52 to 2.92 mm/year]; p = 0.008) and were nearly 3× as likely to experience AAA repair or rupture (15.3% vs. 5.6%; log-rank p = 0.043).ConclusionsFluorine-18-NaF PET-CT is a novel and promising approach to the identification of disease activity in patients with AAA and is an additive predictor of aneurysm growth and future clinical events. (Sodium Fluoride Imaging of Abdominal Aortic Aneurysms [SoFIA3]; NCT02229006; Magnetic Resonance Imaging [MRI] for Abdominal Aortic Aneurysms to Predict Rupture or Surgery: The MA3RS Trial; ISRCTN76413758).
| S-EPMC5800891 | biostudies-literature
Project description:Purpose [18F]Sodium fluoride (NaF) positron emission tomography (PET)/computed tomography (CT) is a promising radiotracer for quantitative assessment of bone metastases. This study assesses changes in early NaF PET/CT response measures in metastatic prostate cancer for correlation to clinical outcomes. Patients and Methods Fifty-six patients with metastatic castration-resistant prostate cancer (mCRPC) with osseous metastases had NaF PET/CT scans performed at baseline and after three cycles of chemotherapy (n = 16) or androgen receptor pathway inhibitors (n = 40). A novel technology, Quantitative Total Bone Imaging, was used for analysis. Global imaging metrics, including maximum standardized uptake value (SUVmax) and total functional burden (SUVtotal), were extracted from composite lesion-level statistics for each patient and tracked throughout treatment. Progression-free survival (PFS) was calculated as a composite end point of progressive events using conventional imaging and/or physician discretion of clinical benefit; NaF imaging was not used for clinical evaluation. Cox proportional hazards regression analyses were conducted between imaging metrics and PFS. Results Functional burden (SUVtotal) assessed midtreatment was the strongest univariable PFS predictor (hazard ratio, 1.97; 95% CI, 1.44 to 2.71; P < .001). Classification of patients based on changes in functional burden showed stronger correlation to PFS than did the change in number of lesions. Various global imaging metrics outperformed baseline clinical markers in predicting outcome, including SUVtotal and SUVmean. No differences in imaging response or PFS correlates were found for different treatment cohorts. Conclusion Quantitative total bone imaging enables comprehensive disease quantification on NaF PET/CT imaging, showing strong correlation to clinical outcomes. Total functional burden assessed after three cycles of hormonal therapy or chemotherapy was predictive of PFS for men with mCRPC. This supports ongoing development of NaF PET/CT-based imaging biomarkers in mCRPC to bone.
| S-EPMC5562173 | biostudies-literature
Project description:BackgroundReliable methods for predicting myocardial infarction in patients with established coronary artery disease are lacking. Coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) provides an assessment of atherosclerosis activity.ObjectivesThis study assessed whether 18F-NaF PET predicts myocardial infarction and provides additional prognostic information to current methods of risk stratification.MethodsPatients with known coronary artery disease underwent 18F-NaF PET computed tomography and were followed up for fatal or nonfatal myocardial infarction over 42 months (interquartile range: 31 to 49 months). Total coronary 18F-NaF uptake was determined by the coronary microcalcification activity (CMA).ResultsIn a post hoc analysis of data collected for prospective observational studies, the authors studied 293 study participants (age: 65 ± 9 years; 84% men), of whom 203 (69%) showed increased coronary 18F-NaF activity (CMA >0). Fatal or nonfatal myocardial infarction occurred only in patients with increased coronary 18F-NaF activity (20 of 203 with a CMA >0 vs. 0 of 90 with a CMA of 0; p < 0.001). On receiver operator curve analysis, fatal or nonfatal myocardial infarction prediction was highest for 18F-NaF CMA, outperforming coronary calcium scoring, modified Duke coronary artery disease index and Reduction of Atherothrombosis for Continued Health (REACH) and Secondary Manifestations of Arterial Disease (SMART) risk scores (area under the curve: 0.76 vs. 0.54, 0.62, 0.52, and 0.54, respectively; p < 0.001 for all). Patients with CMA >1.56 had a >7-fold increase in fatal or nonfatal myocardial infarction (hazard ratio: 7.1; 95% confidence interval: 2.2 to 25.1; p = 0.003) independent of age, sex, risk factors, segment involvement and coronary calcium scores, presence of coronary stents, coronary stenosis, REACH and SMART scores, the Duke coronary artery disease index, and recent myocardial infarction.ConclusionsIn patients with established coronary artery disease, 18F-NaF PET provides powerful independent prediction of fatal or nonfatal myocardial infarction.
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