Project description:BackgroundMicrocalcifications 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 resultsThe 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.ConclusionThe 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.
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:BackgroundMicrocalcifications in atherosclerotic plaques are destabilizing, predict adverse cardiovascular events, and are associated with increased morbidity and mortality.18F-fluoride positron emission tomography (PET)/computed tomography (CT) imaging has demonstrated promise as a useful clinical diagnostic tool in identifying high-risk plaques; however, there is confusion as to the underlying mechanism of signal amplification seen in PET-positive, CT-negative image regions. This study tested the hypothesis that 18F-fluoride PET/CT can identify early microcalcifications.Methods18F-fluoride signal amplification derived from microcalcifications was validated against near-infrared fluorescence molecular imaging and histology using an in vitro 3-dimensional hydrogel collagen platform, ex vivo human specimens, and a mouse model of atherosclerosis.ResultsMicrocalcification size correlated inversely with collagen concentration. The 18F-fluoride ligand bound to microcalcifications formed by calcifying vascular smooth muscle cell derived extracellular vesicles in the in vitro 3-dimensional collagen system and exhibited an increasing signal with an increase in collagen concentration (0.25 mg/mL collagen -33.8×102±12.4×102 counts per minute; 0.5 mg/mL collagen -67.7×102±37.4×102 counts per minute; P=0.0014), suggesting amplification of the PET signal by smaller microcalcifications. We further incubated human atherosclerotic endarterectomy specimens with clinically relevant concentrations of 18F-fluoride. The 18F-fluoride ligand labeled microcalcifications in PET-positive, CT-negative regions of explanted human specimens as evidenced by 18F-fluoride PET/CT imaging, near-infrared fluorescence, and histological analysis. Additionally, the 18F-fluoride ligand identified micro and macrocalcifications in atherosclerotic aortas obtained from low-density lipoprotein receptor-deficient mice.ConclusionsOur results suggest that 18F-fluoride PET signal in PET-positive, CT-negative regions of human atherosclerotic plaques is the result of developing microcalcifications, and high surface area in regions of small microcalcifications may amplify PET signal.
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.
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.
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.
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.
Project description:Inflammation plays an important role in the development of atherosclerosis and its complications. Because the folate receptor β (FR-β) is selectively expressed on macrophages, an FR targeted imaging agent could be useful for assessment of atherosclerotic inflammation. We investigated aluminum fluoride-18-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid conjugated folate (18F-FOL) for the detection of atherosclerotic plaque inflammation. We studied atherosclerotic plaques in mice, rabbits, and human tissue samples using 18F-FOL positron emission tomography/computed tomography (PET/CT). Compound 2-deoxy-2-[18F]fluoro-D-glucose (18F-FDG) was used as a comparison. Firstly, we found that the in vitro binding of 18F-FOL co-localized with FR-β-positive macrophages in carotid endarterectomy samples from patients with recent ischemic symptoms. We then demonstrated specific accumulation of intravenously administered 18F-FOL in atherosclerotic plaques in mice and rabbits using PET/CT. We noticed that the 18F-FOL uptake correlated with the density of macrophages in plaques and provided a target-to-background ratio as high as 18F-FDG, but with considerably lower myocardial uptake. Thus, 18F-FOL PET/CT targeting of FR-β-positive macrophages presents a promising new tool for the in vivo imaging of atherosclerotic inflammation.
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.
Project description:Given the high sensitivity and specificity of sodium [18F]Fluoride (Na[18F]F) for vascular calcifications and positive emerging data of vitamin K on vascular health, the aim of this study is to assess the ability of Na[18F]F to monitor therapy and disease progression in a unitary atherosclerotic mouse model. ApoE-/- mice were placed on a Western-type diet for 12-weeks and then split into four groups. The early stage atherosclerosis group received a chow diet for an additional 12-weeks, while the advanced atherosclerosis group continued the Western-type diet. The Menaquinone-7 (MK-7) and Warfarin groups received MK-7 or Warfarin supplementation during the additional 12-weeks, respectively. Control wild type mice were fed a chow diet for 24-weeks. All of the mice were scanned with Na[18F]F using a small animal positron emission tomography (PET)/computed tomography (CT). The Warfarin group presented spotty calcifications on the CT in the proximal aorta. All of the spots corresponded to dense mineralisations on the von Kossa staining. After the control, the MK-7 group had the lowest Na[18F]F uptake. The advanced and Warfarin groups presented the highest uptake in the aortic arch and left ventricle. The advanced stage group did not develop spotty calcifications, however Na[18F]F uptake was still observed, suggesting the presence of micro-calcifications. In a newly applied mouse model, developing spotty calcifications on CT exclusively in the proximal aorta, Na[18F]F seems to efficiently monitor plaque progression and the beneficial effects of vitamin K on cardiovascular disease.