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Purpose Resveratrol has shown promising anti-inflammatory effects in in vitro and animal studies. We aimed to investigate this effect on arterial inflammation in vivo. Methods This was an additional analysis of a double-blind randomized crossover trial which included eight male subjects with decreased insulin sensitivity who underwent an 18F-fluoroxyglucose (18F-FDG) PET/CT after 34 days of placebo and resveratrol treatment (150 mg/day). 18F-FDG uptake was analyzed in the carotid arteries and the aorta, adipose tissue regions, spleen, and bone marrow as measures for arterial and systemic inflammation. Maximum target-to-background ratios (TBRmax) were compared between resveratrol and placebo treatment with the non-parametric Wilcoxon signed-rank test. Median values are shown with their interquartile range. Results Arterial 18F-FDG uptake was non-significantly higher after resveratrol treatment (TBRmax all vessels 1.7 (1.6–1.7)) in comparison to placebo treatment (1.5 (1.4–1.6); p=0.050). Only in visceral adipose tissue, the increase in 18F-FDG uptake after resveratrol reached statistical significance (p=0.024). Furthermore, CRP-levels were not significantly affected by resveratrol treatment (p=0.091). Conclusions Resveratrol failed to attenuate arterial or systemic inflammation as measured with 18F-FDG PET in subjects at risk of developing type 2 diabetes. However, validation of these findings in larger human studies is needed.

Cardiotoxicity may present as (pulmonary) hypertension, acute and chronic coronary syndromes, venous thromboembolism, cardiomyopathies/heart failure, arrhythmia, valvular heart disease, peripheral arterial disease, and myocarditis. Many of these disease entities can be diagnosed by established cardiovascular diagnostic pathways. Nuclear medicine, however, has proven promising in the diagnosis of cardiomyopathies/heart failure, and peri- and myocarditis as well as arterial inflammation. This article first outlines the spectrum of cardiotoxic cancer therapies and the potential side effects. This will be complemented by the definition of cardiotoxicity using non-nuclear cardiovascular imaging (echocardiography, CMR) and biomarkers. Available nuclear imaging techniques are then presented and specific suggestions are made for their application and potential role in the diagnosis of cardiotoxicity. Correction to: European Journal of Nuclear Medicine and Molecular Imaginghttps://doi.org/10.1007/s00259-022-05991-7The authors regret that their names in the original article are incorrect as the first and last names were interchanged. It is now corrected in erratum article.

With this summarized document we share the standard for positron emission tomography (PET)/(diagnostic)computed tomography (CT) imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is) as recently published in the European Journal of Nuclear Medicine and Molecular Imaging. This standard should be applied in clinical practice and integrated in clinical (multicentre) trials for optimal standardization of the procedurals and interpretations. A major focus is put on procedures using [18F]-2-fluoro-2-deoxyglucose ([18F]FDG), but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this summarized document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicentre trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Diagnosis and management of 4Is related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/magnetic resonance, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.

INTRODUCTION: Vitamin K antagonists (VKA) and non-vitamin K oral antagonist anticoagulants (NOAC) are used in the clinic to reduce risk of thrombosis. However, they also exhibit vascular off-target effects. The aim of this study is to compare VKA and NOAC on atherosclerosis progression and calcification in an experimental setup.MATERIAL AND METHODS: Female Apoe-/- mice (age 12 weeks) were fed Western-type diet as control or supplemented with dabigatran etexilate or warfarin for 6 or 18 weeks. Vascular calcification was measured in whole aortic arches using µCT and [18 F]-NaF. Atherosclerotic burden was assessed by (immuno)histochemistry. Additionally, in vitro effects of warfarin, thrombin, and dabigatran on primary vascular smooth muscle cells (VSMC) were assessed.RESULTS: Short-term treatment with warfarin promoted formation of atherosclerotic lesions with a pro-inflammatory phenotype, and more rapid plaque progression compared with control and dabigatran. In contrast, dabigatran significantly reduced plaque progression compared with control. Long-term warfarin treatment significantly increased both presence and activity of plaque calcification compared with control and dabigatran. Calcification induced by warfarin treatment was accompanied by increased presence of uncarboxylated matrix Gla protein. In vitro, both warfarin and thrombin significantly increased VSMC oxidative stress and extracellular vesicle release, which was prevented by dabigatran.CONCLUSION: Warfarin aggravates atherosclerotic disease activity, increasing plaque inflammation, active calcification, and plaque progression. Dabigatran lacks undesired vascular side effects and reveals beneficial effects on atherosclerosis progression and calcification. The choice of anticoagulation impacts atherosclerotic disease by differential off target effect. Future clinical studies should test whether this beneficial effect also applies to patients.

in press A consensus statement about indications for post-surgical radioiodine therapy (RIT) in differentiated thyroid cancer patients (DTC) was recently published by the European Thyroid Association (ETA) 1. This publication discusses indications for RIT on the basis of an individual risk assessment. Many of the conclusions of this consensus statement are well founded and accepted across the disciplines involved. However, especially from the perspective of nuclear medicine, as the discipline responsible for indicating and executing RIT, some of the recommendations may require further clarification with regard to their compatibility with established best practice and national standards of care. Assessment of the indications for RIT is strongly dependent on the weighing up of benefits and risks. On the basis of longstanding clinical experience in nuclear medicine, RIT represents a highly specific precision medicine procedure of proven efficacy with a favorable side-effect profile. This distinguishes RIT significantly from other adjuvant oncological therapies and has resulted in the establishment of this procedure as a usually well-tolerated, standard safety measure. With regard to its favorable risk/benefit ratio, this procedure should not be unnecessarily restricted, in the interest of offering reassurance to the patients. Both patients' interests and regional/national differences need to be taken into account. We would therefore like to comment on the recent consensus from the perspective of authors and to provide recommendations based on the respective published data.

With this document, we provide a standard for PET/(diagnostic) CT imaging procedures in cardiovascular diseases that are inflammatory, infective, infiltrative, or associated with dysfunctional innervation (4Is). This standard should be applied in clinical practice and integrated in clinical (multicenter) trials for optimal procedural standardization. A major focus is put on procedures using [18F]FDG, but 4Is PET radiopharmaceuticals beyond [18F]FDG are also described in this document. Whilst these novel tracers are currently mainly applied in early clinical trials, some multicenter trials are underway and we foresee in the near future their use in clinical care and inclusion in the clinical guidelines. Finally, PET/MR applications in 4Is cardiovascular diseases are also briefly described. Diagnosis and management of 4Is-related cardiovascular diseases are generally complex and often require a multidisciplinary approach by a team of experts. The new standards described herein should be applied when using PET/CT and PET/MR, within a multimodality imaging framework both in clinical practice and in clinical trials for 4Is cardiovascular indications.

The development of neurodegenerative diseases is associated with cerebral inflammation, which activates resident immune cells of the central nervous system (CNS), namely microglial cells that show an up-regulation of the cannabinoid subtype 2 receptor (CB2R) expression. Therefore our work aimed to design and synthesize a radiotracer for the detection of CB2R expression by positron emission tomography (PET) allowing an early diagnosis of neurodegenerative diseases. For the development of such a PET tracer, N-alkyl-substituted indole-3-yl-tetramethylcyclopropylketones served as lead structures due to their high CB2R potency and selectivity, allowing radiolabeling on the N-alkyl chain. To this end, eight novel fluorinated N-alkyl-indole-3-yl-tetramethylcyclopropylketones were synthesized, investigated in radioligand binding studies, and structure-activity relationships were evaluated. The most promising candidate was (1-(4-fluoropropyl)-1H-indole-3-yl)(2,2,3,3-tetramethyl-cyclopropyl)methanone (Ki: 7.88 nM at the CB2R, 3430 nM at cannabinoid subtype 1 receptor (CB1R)). A precursor was synthesized, radiofluorinated with no-carrier-added [18F]F- by nucleophilic substitution of a tosyl group, and the resulting PET ligand was purified, all being performed on a fully automated synthesis module. The tracer was produced in 34 ± 6% radiochemical yield within 2 h and with molar activities of up to 1500 GBq/μmol. A first preclinical evaluation was carried out including determination of logP, metabolic stability by liver microsomes, and autoradiography. The novel PET tracer for imaging CB2R showed promising results warranting subsequent clinical evaluation.

Cardiovascular disease is responsible for approximately 33 % of all deaths in the USA [1]. Coronary artery disease (CAD) is present in 16.3 million adults. In 2008, CAD caused approximately 405,000 deaths in the USA, making it the number one killer. About 1.2 million people will suffer a new or recurrent heart attack each year [2].

European journal of nuclear medicine and molecular imaging 46(7), 1428-1438 (2019). doi:10.1007/s00259-019-04292-w, Published by Springer-Verl., Heidelberg [u.a.]

Cardiovascular disease is the major cause of morbidity and mortality in developed countries and atherosclerosis is the major cause of cardiovascular disease. Atherosclerotic lesions obstruct blood flow in the arterial vessel wall and can rupture leading to the formation of occlusive thrombi. Conventional diagnostic tools are still of limited value for identifying the vulnerable arterial plaque and for predicting its risk of rupture and of releasing thromboembolic material. Knowledge of the molecular and biological processes implicated in the process of atherosclerosis will advance the development of imaging probes to differentiate the vulnerable plaque. The development of imaging probes with high sensitivity and specificity in identifying high-risk atherosclerotic vessel wall changes and plaques is crucial for improving knowledge-based decisions and tailored individual interventions. Arterial PET imaging with 18F-FDG has shown promising results in identifying inflammatory vessel wall changes in numerous studies and clinical trials. However, due to its limited specificity in general and its intense physiological uptake in the left ventricular myocardium that impair imaging of the coronary arteries, different PET tracers for the molecular imaging of atherosclerosis have been evaluated. This review describes biological, chemical and medical expertise supporting a translational approach that will enable the development of new or the evaluation of existing PET tracers for the identification of vulnerable atherosclerotic plaques for better risk prediction and benefit to patients.

The use of cardiac PET, and in particular of quantitative myocardial perfusion PET, has been growing during the last years, because scanners are becoming widely available and because several studies have convincingly demonstrated the advantages of this imaging approach. Therefore, there is a need of determining the procedural modalities for performing high-quality studies and obtaining from this demanding technique the most in terms of both measurement reliability and clinical data. Although the field is rapidly evolving, with progresses in hardware and software, and the near perspective of new tracers, the EANM Cardiovascular Committee found it reasonable and useful to expose in an updated text the state of the art of quantitative myocardial perfusion PET, in order to establish an effective use of this modality and to help implementing it on a wider basis. Together with the many steps necessary for the correct execution of quantitative measurements, the importance of a multiparametric approach and of a comprehensive and clinically useful report have been stressed.

Nutrients 13(3), 994 (2021). doi:10.3390/nu13030994 special issue: "Clinical Nutrition / Editorial Board : Ina Bergheim, Section Editor-in-Chief", Published by MDPI, Basel

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&minus, /&minus, 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.

2-[18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) has become part of the worldwide standard of care in oncology. Since a decade, this functional imaging tool has also demonstrated very promising results in inflammatory diseases, especially in large vessel vasculitis and atherosclerosis. Since clinical PET imaging is increasingly used in these two conditions, the aim of this chapter is to assist imaging specialists and clinicians by getting used to the PET imaging procedures and current status in clinical practice for these two vascular inflammatory diseases. General background information, PET technical considerations (including patient’s preparation, imaging protocols, scoring methodology), and diagnostic and prognostic performance, but also response monitoring will be addressed, in the light of recent international expert-based recommendations. Also, in the era of personalized medicine, new hybrid technologies and PET radiotracers are discussed.

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.

Despite significant therapeutic advances, myocardial infarction and stroke, as the clinical consequences of atherosclerosis, are the two most common causes of death in Europe and worldwide.

Background Vagus nerve activation impacts inflammation. Therefore, we hypothesized that vagal nerve stimulation (VNS) influenced arterial wall inflammation as measured by 18F-FDG uptake. Results Ten patients with left-sided VNS for refractory epilepsy were studied during stimulation (VNS-on) and in the hours after stimulation was switched off (VNS-off). In nine patients, 18F-FDG uptake was measured in the right carotid artery, aorta, bone marrow, spleen, and adipose tissue. Target-to-background ratios (TBRs) were calculated to normalize the respective standardized uptake values (SUVs) for venous blood pool activity. Median values are shown with interquartile range and compared using the Wilcoxon signed-rank test. Arterial SUVs tended to be higher during VNS-off than VNS-on [SUVmax all vessels 1.8 (1.5–2.2) vs. 1.7 (1.2–2.0), p = 0.051]. However, a larger difference was found for the venous blood pool at this time point, reaching statistical significance in the vena cava superior [meanSUVmean 1.3 (1.1–1.4) vs. 1.0 (0.8–1.1); p = 0.011], resulting in non-significant lower arterial TBRs during VNS-off than VNS-on. Differences in the remaining tissues were not significant. Insulin levels increased after VNS was switched off [55.0 pmol/L (45.9–96.8) vs. 48.1 pmol/L (36.9–61.8); p = 0.047]. The concurrent increase in glucose levels was not statistically significant [4.8 mmol/L (4.7–5.3) vs. 4.6 mmol/L (4.5–5.2); p = 0.075]. Conclusions Short-term discontinuation of VNS did not show a consistent change in arterial wall 18F-FDG-uptake. However, VNS did alter insulin and 18F-FDG blood levels, possibly as a result of sympathetic activation.

Coronary artery disease (CAD) is a major cause of death and disability. Several diagnostic tests, such as myocardial perfusion scintigraphy (MPS), are accurate for the detection of CAD, as well as having prognostic value for the prediction of cardiovascular events. Nevertheless, the diagnostic and prognostic value of these tests should be cost-effective and should lead to improved clinical outcome. We have reviewed the literature on the cost-effectiveness of MPS in different circumstances: (i) the diagnosis and management of CAD; (ii) comparison with exercise electrocardiography (ECG) and other imaging tests; (iii) as gatekeeper to invasive coronary angiography (ICA), (iv) the impact of appropriate use criteria; (v) acute chest pain, and (vi) screening of asymptomatic patients with type-2 diabetes. In total 57 reports were included. Although most non-invasive imaging tests are cost-effective compared with alternatives, the data conflict on which non-invasive strategy is the most cost-effective. Different definitions of cost-effectiveness further confound the subject. Computer simulations of clinical diagnosis and management are influenced by the assumptions made. For instance, diagnostic accuracy is often defined against an anatomical standard that is wrongly assumed to be perfect. Conflicting data arise most commonly from these incorrect or differing assumptions.

The trade-off between resolution and count sensitivity dominates the performance of standard gamma cameras and dictates the need for relatively high doses of radioactivity of the used radiopharmaceuticals in order to limit image acquisition duration. The introduction of cadmium-zinc-telluride (CZT)-based cameras may overcome some of the limitations against conventional gamma cameras. CZT cameras used for the evaluation of myocardial perfusion have been shown to have a higher count sensitivity compared to conventional single photon emission computed tomography (SPECT) techniques. CZT image quality is further improved by the development of a dedicated three-dimensional iterative reconstruction algorithm, based on maximum likelihood expectation maximization (MLEM), which corrects for the loss in spatial resolution due to line response function of the collimator. All these innovations significantly reduce imaging time and result in a lower patient's radiation exposure compared with standard SPECT. To guide current and possible future users of the CZT technique for myocardial perfusion imaging, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, has decided to examine the current literature regarding procedures and clinical data on CZT cameras. The committee hereby aims 1) to identify the main acquisitions protocols; 2) to evaluate the diagnostic and prognostic value of CZT derived myocardial perfusion, and finally 3) to determine the impact of CZT on radiation exposure.

Selective internal radio therapy (SIRT) with Y-90-glass microspheres was performed in a cirrhotic patient with hepatocellular carcinoma (Barcelona Clinic Liver Cancer stage C) after arterial coil embolization for treatment of intratumoral hemorrhage and planned preoperative right portal vein embolization. Three technetium Tc-99m macro-albumin-aggregate injections were needed to optimize intralesional uptake without extrahepatic deposition. The consecutive SIRT treatment was uncomplicated with a remarkable result.

Until recently, PET was regarded as a luxurious way of performing myocardial perfusion scintigraphy, with excellent image quality and diagnostic capabilities that hardly justified the additional cost and procedural effort. Quantitative perfusion PET was considered a major improvement over standard qualitative imaging, because it allows the measurement of parameters not otherwise available, but for many years its use was confined to academic and research settings. In recent years, however, several factors have contributed to the renewal of interest in quantitative perfusion PET, which has become a much more readily accessible technique due to progress in hardware and the availability of dedicated and user-friendly platforms and programs. In spite of this evolution and of the growing evidence that quantitative perfusion PET can play a role in the clinical setting, there are not yet clear indications for its clinical use. Therefore, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, decided to examine the current literature on quantitative perfusion PET to (1) evaluate the rationale for its clinical use, (2) identify the main methodological requirements, (3) identify the remaining technical difficulties, (4) define the most reliable interpretation criteria, and finally (5) tentatively delineate currently acceptable and possibly appropriate clinical indications. The present position paper must be considered as a starting point aiming to promote a wider use of quantitative perfusion PET and to encourage the conception and execution of the studies needed to definitely establish its role in clinical practice.

Background Atherosclerosis is an inflammatory condition with calcification apparent late in the disease process. The extent and progression of coronary calcification predict cardiovascular events. Relatively little is known about noncoronary vascular calcification. Objectives This study investigated noncoronary vascular calcification and its influence on changes in vascular inflammation. Methods A total of 130 participants in the dal-PLAQUE (Safety and efficacy of dalcetrapib on atherosclerotic disease using novel non-invasive multimodality imaging) study underwent fluorodeoxyglucose positron emission tomography/computed tomography at entry and at 6 months. Calcification of the ascending aorta, arch, carotid, and coronary arteries was quantified. Cardiovascular risk factors were related to arterial calcification. The influences of baseline calcification and drug therapy (dalcetrapib vs. placebo) on progression of calcification were determined. Finally, baseline calcification was related to changes in vascular inflammation. Results Age >65 years old was consistently associated with higher baseline calcium scores. Arch calcification trended to progress more in those with calcification at baseline (p = 0.055). There were no significant differences between progression of vascular calcification with dalcetrapib compared to that with placebo. Average carotid target-to-background ratio indexes declined over 6 months if carotid calcium was absent (single hottest slice [p = 0.037], mean of maximum target-to-background ratio [p = 0.010], and mean most diseased segment [p Conclusions Across multiple arterial regions, higher age is consistently associated with higher calcium scores. The presence of vascular calcification at baseline is associated with progressive calcification; in the carotid arteries, calcification appears to influence vascular inflammation. Dalcetrapib therapy did not affect vascular calcification.

Background: 18 F-Fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) was recently introduced as a new tool for the diagnosis of prosthetic heart valve endocarditis (PVE). Previous studies reporting a modest diagnostic accuracy may have been hampered by unstandardized image acquisition and assessment, and several confounders, as well. The aim of this study was to improve the diagnostic performance of FDG PET/CT in patients in whom PVE was suspected by identifying and excluding possible confounders, using both visual and standardized quantitative assessments. Methods: In this multicenter study, 160 patients with a prosthetic heart valve (median age, 62 years [43–73]; 68% male; 82 mechanical valves; 62 biological; 9 transcatheter aortic valve replacements; 7 other) who underwent FDG PET/CT for suspicion of PVE, and 77 patients with a PV (median age, 73 years [65–77]; 71% male; 26 mechanical valves; 45 biological; 6 transcatheter aortic valve replacements) who underwent FDG PET/CT for other indications (negative control group), were retrospectively included. Their scans were reassessed by 2 independent observers blinded to all clinical data, both visually and quantitatively on available European Association of Nuclear Medicine Research Ltd–standardized reconstructions. Confounders were identified by use of a logistic regression model and subsequently excluded. Results: Visual assessment of FDG PET/CT had a sensitivity/specificity/positive predictive value/negative predictive value for PVE of 74%/91%/89%/78%, respectively. Low inflammatory activity (C-reactive protein Conclusions: Both visual and quantitative assessments of FDG PET/CT have a high diagnostic accuracy in patients in whom PVE is suspected. FDG PET/CT should be implemented early in the diagnostic workup to prevent the negative confounding effects of low inflammatory activity (eg, attributable to prolonged antibiotic therapy). Recent valve implantation was not a significant predictor of false-positive interpretations, but surgical adhesives used during implantation were.

In this multicenter study, 160 patients with a prosthetic heart valve (median age, 62 years [43-73]; 68% male; 82 mechanical valves; 62 biological; 9 transcatheter aortic valve replacements; 7 other) who underwent FDG PET/CT for suspicion of PVE, and 77 patients with a PV (median age, 73 years [65-77]; 71% male; 26 mechanical valves; 45 biological; 6 transcatheter aortic valve replacements) who underwent FDG PET/CT for other indications (negative control group), were retrospectively included. Their scans were reassessed by 2 independent observers blinded to all clinical data, both visually and quantitatively on available European Association of Nuclear Medicine Research Ltd-standardized reconstructions. Confounders were identified by use of a logistic regression model and subsequently excluded.Visual assessment of FDG PET/CT had a sensitivity/specificity/positive predictive value/negative predictive value for PVE of 74%/91%/89%/78%, respectively. Low inflammatory activity (C-reactive protein40 mg/L) at the time of imaging and use of surgical adhesives during prosthetic heart valve implantation were significant confounders, whereas recent valve implantation was not. After the exclusion of patients with significant confounders, diagnostic performance values of the visual assessment increased to 91%/95%/95%/91%. As a semiquantitative measure of FDG uptake, a European Association of Nuclear Medicine Research Ltd-standardized uptake value ratio of ≥2.0 was a 100% sensitive and 91% specific predictor of PVE.Both visual and quantitative assessments of FDG PET/CT have a high diagnostic accuracy in patients in whom PVE is suspected. FDG PET/CT should be implemented early in the diagnostic workup to prevent the negative confounding effects of low inflammatory activity (eg, attributable to prolonged antibiotic therapy). Recent valve implantation was not a significant predictor of false-positive interpretations, but surgical adhesives used during implantation were.

BASIK2 is a prospective, double-blind, randomized placebo-controlled trial investigating the effect of vitamin K2 (menaquinone-7;MK7) on imaging measurements of calcification in the bicuspid aortic valve (BAV) and calcific aortic valve stenosis (CAVS). BAV is associated with early development of CAVS. Pathophysiologic mechanisms are incompletely defined, and the only treatment available is valve replacement upon progression to severe symptomatic stenosis. Matrix Gla protein (MGP) inactivity is suggested to be involved in progression. Being a vitamin K dependent protein, supplementation with MK7 is a pharmacological option for activating MGP and intervening in the progression of CAVS. Forty-four subjects with BAV and mild-moderate CAVS will be included in the study, and baseline F-18-sodiumfluoride (F-18-NaF) positron emission tomography (PET)/ magnetic resonance (MR) and computed tomography (CT) assessments will be performed. Thereafter, subjects will be randomized (1:1) to MK7 (360 mcg/day) or placebo. During an 18-month follow-up period, subjects will visit the hospital every 6 months, undergoing a second F-18-NaF PET/MR after 6 months and CT after 6 and 18 months. The primary endpoint is the change in PET/MR F-18-NaF uptake (6 months minus baseline) compared to this delta change in the placebo arm. The main secondary endpoints are changes in calcium score (CT), progression of the left ventricularremodeling response and CAVS severity (echocardiography). We will also examine the association between early calcification activity (PET) and later changes in calcium score (CT).

Atherosclerotic events are usually acute and often strike otherwise asymptomatic patients. Although multiple clinical risk factors have been associated with atherosclerosis, as of yet no further individual prediction can be made as to who will suffer from its consequences based on biomarker analysis or traditional imaging methods like CT, MRI or angiography.Previously, non-invasive imaging with F-18-fluorodeoxyglucose (F-18-FDG) PET was shown to potentially fill this niche as it offers high sensitive detection of metabolic processes associated with inflammatory changes in atherosclerotic plaques. However, F-18-FDG PET imaging of arterial vessels suffers from non specificity and has still to be proven to reliably identify vulnerable plaques, carrying a high risk of rupture. Therefore, it may be regarded only as a secondary marker for monitoring treatment effects and it does not offer alternative treatment options or direct insight in treatment mechanisms.In this review, an overview is given of the current status and the potential of PET imaging of inflammation and angiogenesis in atherosclerosis in general and special emphasis is given to imaging of alpha 7 nicotinic acetylcholine receptors (alpha 7 nAChRs). Due to the gaps that still exist in our understanding of atherogenesis and the limitations of the available PET tracers, the search continues for a more specific radioligand, able to differentiate between stable atherosclerosis and plaques prone to rupture. The potential role of the alpha 7 nAChR as imaging marker for plaque vulnerability is explored. Today, strong evidence exists that nAChRs are involved in the atherosclerotic disease process. They are suggested to mediate the deleterious effects of the major tobacco component, nicotine, a nAChR agonist.Mainly based on in vitro data, alpha 7 nAChR stimulation might increase plaque burden via increased neovascularization. However, in animal studies, alpha 7 nAChR manipulation appears to reduce plaque size due to its inhibitory effects on inflammatory cells. Thus, reliable identification of alpha 7 nAChRs by in vivo imaging is crucial to investigate the exact role of alpha 7 nAChR in atherosclerosis before any therapeutic approach in the human setting can be justified.In this review, we discuss the first experience with alpha 7 nAChR PET tracers and developmental considerations regarding the "optimal" PET tracer to image vascular nAChRs. (C) 2017 Published by Elsevier Inc.

European journal of nuclear medicine and molecular imaging 42(9), 1423-1429 (2015). doi:10.1007/s00259-015-3081-y, Published by Springer-Verl., Heidelberg [u.a.]

Coronary artery disease (CAD) is a major cause of death and disability. Several diagnostic tests, such as myocardial perfusion scintigraphy (MPS), are accurate for the detection of CAD, as well as having prognostic value for the prediction of cardiovascular events. Nevertheless, the diagnostic and prognostic value of these tests should be cost-effective and should lead to improved clinical outcome. We have reviewed the literature on the cost-effectiveness of MPS in different circumstances: (i) the diagnosis and management of CAD; (ii) comparison with exercise electrocardiography (ECG) and other imaging tests; (iii) as gatekeeper to invasive coronary angiography (ICA), (iv) the impact of appropriate use criteria; (v) acute chest pain, and (vi) screening of asymptomatic patients with type-2 diabetes. In total 57 reports were included. Although most non-invasive imaging tests are cost-effective compared with alternatives, the data conflict on which non-invasive strategy is the most cost-effective. Different definitions of cost-effectiveness further confound the subject. Computer simulations of clinical diagnosis and management are influenced by the assumptions made. For instance, diagnostic accuracy is often defined against an anatomical standard that is wrongly assumed to be perfect. Conflicting data arise most commonly from these incorrect or differing assumptions.

European journal of nuclear medicine and molecular imaging 44(7), 1234-1243 (2017). doi:10.1007/s00259-017-3675-7, Published by Springer-Verl., Heidelberg [u.a.]

European journal of nuclear medicine and molecular imaging 44(7), 1119-1128 (2017). doi:10.1007/s00259-017-3651-2, Published by Springer-Verl., Heidelberg [u.a.]

SummaryBackgroundFat tissue, and particularly visceral fat, is known to play a role in low grade systemic inflammation in COPD, and is likely to contribute to the excess cardiovascular comorbidity in COPD. Therefore, we aimed to study 18FDG-PET-assessed inflammation of the aorta and the (visceral) fat, and evaluate its interrelations and differences in subjects with and without COPD.MethodsWe retrospectively identified 42 patients (71% male, 48% current smokers, mean age 66.6 ± 8.3 years, mean BMI 25.1 ± 4.3 kg/m2), who underwent 18F-FDG-PET/CT for suspected early stage bronchus carcinoma. COPD-diagnosis was based on spirometry and defined as FEV1/FVC

PURPOSE: Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. METHODS: This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. RESULTS: Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, 18F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to 18F-FDG, other radiopharmaceuticals such as 99mTc-sestamibi, 123I-metaiodobenzylguanidine (MIBG), 18F-fluorodopa and 18F-14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. CONCLUSION: Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity.

Baseline predictors of response to treatment of patients with coronary heart disease (CHD) with respect to vascular inflammation and atherosclerotic plaque burden are poorly understood. From post hoc analysis of the dal-PLAQUE study (NCT00655473), 18F-fluorodeoxyglucose-positron emission tomography (18-FDG-PET) imaging and carotid black blood magnetic resonance imaging (MRI) were used to track changes in these vascular parameters. Baseline demographics, imaging, and biomarkers were collected/measured in 130 patients with CHD or CHD risk-equivalents, and imaging follow-up at 6 months (PET) and 24 months (MRI) was performed. Using stepwise linear regression, predictors of change in carotid plaque inflammation by PET [target-to-background ratio (TBR), n = 92] and plaque burden by MRI [wall area (WA) and total vessel area (TVA), n = 89] were determined. Variables with p

PURPOSE: The purpose of this paper is to study molecular imaging of apoptosis and necrosis, two key players in atherosclerosis instability, using a multimodal imaging approach combining single photon emission computed tomography (SPECT), positron emission tomography (PET), and computed tomography (CT). PROCEDURES: Collar-induced carotid atherosclerosis ApoE knockout mice were imaged with 99mTc-AnxAF568 SPECT-CT to study apoptosis and sequentially with PET-CT following 124I-Hypericin (124I-Hyp) injection to visualize necrosis. RESULTS: SPECT depicted increased 99mTc-AnxAF568 uptake in both atherosclerotic carotid arteries, whereas our data suggest that this uptake is not merely apoptosis related. Although PET of 124I-Hyp was hampered by the slow blood clearance in atherosclerotic mice, 124I-Hyp was able to target necrosis in the atherosclerotic plaque. CONCLUSION: Both 99mTc-AnxAF568 and 124I-Hyp uptake are increased in atherosclerotic carotid vasculature compared to control arteries. While apoptosis imaging remains challenging, necrosis imaging can be feasible after improving the biodistribution characteristics of the probe.

PURPOSE: To compare pretherapy (124)I PET/CT and posttherapy (131)I SPECT/CT in the identification of pathological lesions and the staging of patients with differentiated thyroid carcinoma. METHODS: (124)I SPECT with low-dose CT in addition to a standard whole-body scan was performed 5 days following (131)I therapy with the administration of 1,110-7,728 MBq. Pretherapy (124)I PET/CT was done 24 h and 96 h after oral ingestion of 20-28 MBq, including a noncontrast high-dose CT scan. Scans were evaluated by two independent experienced nuclear physicians. In addition to the total number of lesions found, patient-based analyses and lesion-based analyses were performed to ascertain the discrepancies between the findings of the two scanning techniques, as well as to evaluate the clinical impact of the findings. RESULTS: A group of 20 consecutive patients were analysed. In the lesion-based analysis, a total of 62 foci were found with all modalities together. Of these, (124)I PET/CT found 57 (92 %), (131)I SPECT/CT 50 (81 %) and planar imaging 39 (63 %). In the patient-based analysis, in 50 % of patients complete concordance between the findings of (124)I PET and (131)I SPECT was seen, in 5 % complete discordance and in the remaining 45 % partial discordance, i.e. a focus or some foci seen with both modalities but another or others seen more or less with one or other modality. In 5 of the 20 patients (25 %), tumour stage was changed according to the findings of one of the modalities. In 60 % of these patients this was only with the findings of (124)I PET/CT. CONCLUSION: This study showed that (124)I PET/CT is preferred over (131)I imaging for staging differentiated thyroid carcinoma.

Whereas in the past the term "vasculitis" was most frequently used in context with systemic vasculitides, such as the large vessel vasculitides (LVV) Takayasa arteritis and giant cell arteritis, characterized by inflammation of blood vessel walls, it nowadays comprises also inflammatory changes of the vessel wall as a substantial part of the atherosclerotic disease process. Implementing non-invasive imaging techniques, such as computed tomography angiography (CTA), magnetic resonance angiography (MRA) as well as positron emission tomography (PET) in the diagnostic algorithm of atherosclerosis and LVV, depicts a promising step towards an earlier detection with a, consecutively, improved therapeutic approach and potentially prognostic benefit in patients suffering from vasculitis. Mainly molecular imaging with 18F-fluorodeoxyglucose (FDG) PET seems to be promising in offering an early and sensitive identification of inflammatory changes in both, atherosclerosis and LVV. This review will therefore provide an overview on the diagnostic performance and clinical relevance of FDG-PET in monitoring vasculitis in atherosclerosis and LVV, with a focus on LVV.