24 research outputs found

    Targeted Molecular Imaging in Adrenal Disease—An Emerging Role for Metomidate PET-CT

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    Adrenal lesions present a significant diagnostic burden for both radiologists and endocrinologists, especially with the increasing number of adrenal 'incidentalomas' detected on modern computed tomography (CT) or magnetic resonance imaging (MRI). A key objective is the reliable distinction of benign disease from either primary adrenal malignancy (e.g., adrenocortical carcinoma or malignant forms of pheochromocytoma/paraganglioma (PPGL)) or metastases (e.g., bronchial, renal). Benign lesions may still be associated with adverse sequelae through autonomous hormone hypersecretion (e.g., primary aldosteronism, Cushing's syndrome, phaeochromocytoma). Here, identifying a causative lesion, or lateralising the disease to a single adrenal gland, is key to effective management, as unilateral adrenalectomy may offer the potential for curing conditions that are typically associated with significant excess morbidity and mortality. This review considers the evolving role of positron emission tomography (PET) imaging in addressing the limitations of traditional cross-sectional imaging and adjunctive techniques, such as venous sampling, in the management of adrenal disorders. We review the development of targeted molecular imaging to the adrenocortical enzymes CYP11B1 and CYP11B2 with different radiolabeled metomidate compounds. Particular consideration is given to iodo-metomidate PET tracers for the diagnosis and management of adrenocortical carcinoma, and the increasingly recognized utility of 11^{11}C-metomidate PET-CT in primary aldosteronism.NIHR Cambridge Biomedical Research Centr

    Pericoronary and periaortic adipose tissue density are associated with inflammatory disease activity in Takayasu arteritis and atherosclerosis.

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    AimsTo examine pericoronary adipose tissue (PCAT) and periaortic adipose tissue (PAAT) density on coronary computed tomography angiography for assessing arterial inflammation in Takayasu arteritis (TAK) and atherosclerosis.Methods and resultsPCAT and PAAT density was measured in coronary (n = 1016) and aortic (n = 108) segments from 108 subjects [TAK + coronary artery disease (CAD), n = 36; TAK, n = 18; atherosclerotic CAD, n = 32; matched controls, n = 22]. Median PCAT and PAAT densities varied between groups (mPCAT: P P = 0.0002). PCAT density was 7.01 ± standard error of the mean (SEM) 1.78 Hounsfield Unit (HU) higher in coronary segments from TAK + CAD patients than stable CAD patients (P = 0.0002), and 8.20 ± SEM 2.04 HU higher in TAK patients without CAD than controls (P = 0.0001). mPCAT density was correlated with Indian Takayasu Clinical Activity Score (r = 0.43, P = 0.001) and C-reactive protein (r = 0.41, P P = 0.002). mPCAT density above -74 HU had 100% sensitivity and 95% specificity for differentiating active TAK from controls [area under the curve = 0.99 (95% confidence interval 0.97-1)]. The association of PCAT density and coronary arterial inflammation measured by 68Ga-DOTATATE positron emission tomography (PET) equated to an increase of 2.44 ± SEM 0.77 HU in PCAT density for each unit increase in 68Ga-DOTATATE maximum tissue-to-blood ratio (P = 0.002). These findings remained in multivariable sensitivity analyses adjusted for potential confounders.ConclusionsPCAT and PAAT density are higher in TAK than atherosclerotic CAD or controls and are associated with clinical, biochemical, and PET markers of inflammation. Owing to excellent diagnostic accuracy, PCAT density could be useful as a clinical adjunct for assessing disease activity in TAK

    Detection of Atherosclerotic Inflammation by 68^{68}Ga-DOTATATE PET Compared to [18^{18}F]FDG PET Imaging

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    Background\textbf{Background} Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([18^{18}F]FDG PET), [18^{18}F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. Objectives\textbf{Objectives} Objectives This study tested the efficacy of gallium-68-labeled DOTATATE (68^{68}Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation. Methods\textbf{Methods} We confirmed 68^{68}Ga-DOTATATE binding in macrophages and excised carotid plaques. 68^{68}Ga-DOTATATE PET imaging was compared to [18^{18}F]FDG PET imaging in 42 patients with atherosclerosis. Results\textbf{Results} Target SSTR2\textit{SSTR2} gene expression occurred exclusively in “proinflammatory” M1 macrophages, specific 68^{68}Ga-DOTATATE ligand binding to SST2_{2} receptors occurred in CD68-positive macrophage-rich carotid plaque regions, and carotid SSTR2\textit{SSTR2} mRNA was highly correlated with in vivo 68^{68}Ga-DOTATATE PET signals (r = 0.89; 95% confidence interval [CI]: 0.28 to 0.99; p = 0.02). 68^{68}Ga-DOTATATE mean of maximum tissue-to-blood ratios (mTBRmax_{max}) correctly identified culprit versus nonculprit arteries in patients with acute coronary syndrome (median difference: 0.69; interquartile range [IQR]: 0.22 to 1.15; p = 0.008) and transient ischemic attack/stroke (median difference: 0.13; IQR: 0.07 to 0.32; p = 0.003). 68^{68}Ga-DOTATATE mTBRmax_{max} predicted high-risk coronary computed tomography features (receiver operating characteristics area under the curve [ROC AUC]: 0.86; 95% CI: 0.80 to 0.92; p < 0.0001), and correlated with Framingham risk score (r = 0.53; 95% CI: 0.32 to 0.69; p <0.0001) and [18^{18}F]FDG uptake (r = 0.73; 95% CI: 0.64 to 0.81; p < 0.0001). [18^{18}F]FDG mTBRmax_{max} differentiated culprit from nonculprit carotid lesions (median difference: 0.12; IQR: 0.0 to 0.23; p = 0.008) and high-risk from lower-risk coronary arteries (ROC AUC: 0.76; 95% CI: 0.62 to 0.91; p = 0.002); however, myocardial [18^{18}F]FDG spillover rendered coronary [18^{18}F]FDG scans uninterpretable in 27 patients (64%). Coronary 68^{68}Ga-DOTATATE PET scans were readable in all patients. Conclusions\textbf{Conclusions} We validated 68^{68}Ga-DOTATATE PET as a novel marker of atherosclerotic inflammation and confirmed that 68^{68}Ga-DOTATATE offers superior coronary imaging, excellent macrophage specificity, and better power to discriminate high-risk versus low-risk coronary lesions than [18^{18}F]FDG. (Vascular Inflammation Imaging Using Somatostatin Receptor Positron Emission Tomography [VISION]; NCT02021188)This study was funded by the Wellcome Trust and supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre and the Cambridge Clinical Trials Unit. Dr. Tarkin is supported by a Wellcome Trust research training fellowship (104492/Z/14/Z). Dr. Evans is supported by a Dunhill Medical Trust fellowship (RTF44/0114). Dr. Chowdhury is supported by Royal College of Surgeons of England and British Heart Foundation (BHF) fellowships (FS/16/29/31957). Drs. Manavaki and Warburton are supported by the NIHR Biomedical Research Centres. Drs. Yu and Frontini are supported by the BHF (RE/13/6/30180). Dr. Fryer is supported by Higher Education Funding Council for England (HEFCE). Dr. Groves is supported by the University College London Hospital NIHR Biomedical Research Centre; and has received grant support from GlaxoSmithKline. Dr. Ouwehand’s laboratory is funded by EU-FP7 project Blueprint (Health-F5-2011-282510), BHF (PG-0310-1002 and RG/09/12/28096), and National Health Service Blood and Transplant. Dr. Bennett is supported by NIHR and BHF. Dr. Davenport is supported by research grants from Wellcome Trust (107715/Z/15/Z), Medical Research Council (MC_PC_14116), and BHF (RE-13-6-3180). Dr. Rudd is supported by the NIHR, BHF, Wellcome Trust, and HEFCE

    Imaging tumour hypoxia with positron emission tomography.

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    Hypoxia, a hallmark of most solid tumours, is a negative prognostic factor due to its association with an aggressive tumour phenotype and therapeutic resistance. Given its prominent role in oncology, accurate detection of hypoxia is important, as it impacts on prognosis and could influence treatment planning. A variety of approaches have been explored over the years for detecting and monitoring changes in hypoxia in tumours, including biological markers and noninvasive imaging techniques. Positron emission tomography (PET) is the preferred method for imaging tumour hypoxia due to its high specificity and sensitivity to probe physiological processes in vivo, as well as the ability to provide information about intracellular oxygenation levels. This review provides an overview of imaging hypoxia with PET, with an emphasis on the advantages and limitations of the currently available hypoxia radiotracers.Cancer Research UK (CRUK) funded the National Cancer Research Institute (NCRI) PET Research Working party to organise a meeting to discuss imaging cancer with hypoxia tracers and Positron Emission Tomography. IF was funded by CRUK and is also supported by the Chief Scientific Office. ALH is supported by CRUK and the Breast Cancer Research Foundation. RM is funded by NIHR Cambridge Biomedical Research Centre.This is the accepted manuscript. The final version is available from Nature Publishing at http://www.nature.com/bjc/journal/vaop/ncurrent/full/bjc2014610a.html

    Inter-frame filtering for list-mode EM reconstruction in high-resolution 4-D PET

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