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An increasing number of Nuclear Medicine sites in Europe are using cardiac-centered gamma cameras for myocardial perfusion scintigraphy (MPS). Three cardiac-centered gamma cameras are currently the most frequently used in Europe: the D-SPECT (Spectrum Dynamics), the Alcyone (Discovery NM 530c and Discovery NM/CT 570c; General Electric Medical Systems), and the IQ-SPECT (Siemens Healthcare). The increased myocardial count sensitivity of these three cardiac-centered systems has allowed for a decrease in the activities of radiopharmaceuticals injected to patients for myocardial perfusion imaging and, consequently, radiation exposure of patients. When setting up protocols for MPS, the overall objective should be to maintain high diagnostic accuracy of MPS, while injecting the lowest activities reasonably achievable to reduce the level of radiation exposure of patient and staff. These guidelines aim at providing recommendations for acquisition protocols and image interpretation using cardiac-centered cameras. As each imaging system has specific design and features for image acquisition and analysis, these guidelines have been separated into three sections for each gamma camera system. These recommendations have been written by the members of the Cardiovascular Committee of EANM and were based on their own experience with each of these systems and on the existing literature.

Purpose: We aimed to investigate the influence of both hypothyroidism and thyroid-stimulating hormone (TSH) suppression on vascular inflammation, as assessed with 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT)., Methods: Ten thyroid carcinoma patients underwent an 18 F-FDG PET/CT during post-thyroidectomy hypothyroidism and during thyrotropin (TSH) suppression after 131 I (radioiodine) ablation therapy. We analysed the 18 F-FDG uptake in the carotids, aortic arch, ascending, descending, and abdominal aorta to investigate the effects of thyroid hormone status on arterial inflammation. Target-to-background ratios (TBRs) corrected for blood pool activity were established for all arterial territories. Results were further compared to euthyroid historic control subjects., Results: In general, there was a trend towards higher vascular TBRs during TSH suppression than during hypothyroidism (TBR max all vessels = 1.6 and 1.8, respectively, p = 0.058), suggesting a higher degree of arterial inflammation. In concurrence with this, we found increased C-reactive protein (CRP) levels after levothyroxine treatment (CRP = 2.9 mg/l and 4.8 mg/l, p = 0.005). An exploratory comparison with euthyroid controls showed significant higher TBRs during TSH suppression for the carotids, aortic arch, thoracic descending aorta, and when all vascular territories were combined (TBR max p = 0.013, p = 0.016, p = 0.030 and p = 0.018 respectively)., Conclusions: Arterial inflammation is increased during TSH suppression. This finding sheds new light on the underlying mechanism of the suspected increased risk of cardiovascular disease in patients with TSH suppression.

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 18 F-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.

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 <40 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., 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.

Positron emission tomography (PET) and magnetic resonance imaging (MRI) have both been used for decades in cardiovascular imaging. Since 2010, hybrid PET/MRI using sequential and integrated scanner platforms has been available, with hybrid cardiac PET/MR imaging protocols increasingly incorporated into clinical workflows. Given the range of complementary information provided by each method, the use of hybrid PET/MRI may be justified and beneficial in particular clinical settings for the evaluation of different disease entities. In the present joint position statement, we critically review the role and value of integrated PET/MRI in cardiovascular imaging, provide a technical overview of cardiac PET/MRI and practical advice related to the cardiac PET/MRI workflow, identify cardiovascular applications that can potentially benefit from hybrid PET/MRI, and describe the needs for future development and research. In order to encourage its wide dissemination, this article is freely accessible on the European Radiology and European Journal of Hybrid Imaging web sites., Key Points: • Studies and case-reports indicate that PET/MRI is a feasible and robust technology. • Promising fields of application include a variety of cardiac conditions. • Larger studies are required to demonstrate its incremental and cost-effective value. • The translation of novel radiopharmaceuticals and MR-sequences will provide exciting new opportunities.

The short- and long-term success of intravascular stents depends on a proper re-endothelialisation after the intervention-induced endothelial denudation. The aim of this study was to evaluate the potential of in vivo molecular imaging of glutamate carboxypeptidase II (GCPII; identical with prostate-specific membrane antigen PSMA) expression as a marker of re-endothelialisation. Fifteen Sprague Dawley rats underwent unilateral balloon angioplasty of the common carotid artery (CCA). Positron emission tomography (PET) using the GCPII-targeting tracer [ 18 F]DCFPyL was performed after 5-21 days (scan 60-120 min post injection). In two animals, the GCPII inhibitor PMPA (23 mg/kg BW) was added to the tracer solution. After PET, both CCAs were removed, dissected, and immunostained with the GCPII specific antibody YPSMA-1. Difference of GCPII expression between both CCAs was established by PCR analysis. [ 18 F]DCFPyL uptake was significantly higher in the ipsilateral compared to the contralateral CCA with an ipsi-/contralateral ratio of 1.67 ± 0.39. PMPA blocked tracer binding. The selective expression of GCPII in endothelial cells of the treated CCA was confirmed by immunohistological staining. PCR analysis verified the site-specific GCPII expression. By using a molecular imaging marker of GCPII expression, we provide the first non-invasive in vivo delineation of re-endothelialisation after angioplasty.

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 18 F-sodiumfluoride ( 18 F-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 18 F-NaF PET/MR after 6 months and CT after 6 and 18 months. The primary endpoint is the change in PET/MR 18 F-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)., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the writing of the manuscript.

Selective internal radio therapy (SIRT) with Y-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 macro-albumin-aggregate injections were needed to optimize intralesional uptake without extrahepatic deposition. The consecutive SIRT treatment was uncomplicated with a remarkable result.

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 18 F-fluorodeoxyglucose ( 18 F-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, 18 F-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 α7 nicotinic acetylcholine receptors (α7 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 α7 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, α7 nAChR stimulation might increase plaque burden via increased neovascularization. However, in animal studies, α7 nAChR manipulation appears to reduce plaque size due to its inhibitory effects on inflammatory cells. Thus, reliable identification of α7 nAChRs by in vivo imaging is crucial to investigate the exact role of α7 nAChR in atherosclerosis before any therapeutic approach in the human setting can be justified. In this review, we discuss the first experience with α7 nAChR PET tracers and developmental considerations regarding the "optimal" PET tracer to image vascular nAChRs., (Copyright © 2017. Published by Elsevier Inc.)

Aims: To compare the prognostic value of negative non-invasive cardiac investigations (coronary computed tomographic angiography [CCTA], cardiovascular magnetic resonance [CMR], exercise electrocardiographic testing [EET], positron emission tomography [PET], stress-echocardiography [SE], and single-photon emission tomography [SPECT]) in patients with suspected or known coronary artery disease (CAD) and to explore the effect of adjustment for population event risk and presence of CAD., Methods and Results: MEDLINE/PubMed database, EMBASE and Cochrane Library were searched from January-1990 to April-2015 for studies reporting annual event rates (AER) of myocardial infarction (MI) and cardiac death. Pooled estimates of AERs were calculated using a DerSimonian and Laird random-effects model. Multivariable linear meta-regression analysis was performed to compare the AER after a negative test result between modalities and to adjust for population event risk and proportion of patients with CAD. In 165 studies (122,721 patients), pooled AERs after negative test results differed significantly between modalities ranging from 0.32% for CCTA to 1.66% for SE, P < 0.001. However, the AER after a negative test result was positively correlated (r = 0.726, P < 0.001) with population event risk. Adjusting for population event risk and proportion of patients with CAD resulted in more similar event rates after a negative test result., Conclusion: This meta-analysis is the first study comparing the prognostic value of all available non-invasive cardiac investigations. Outcome differences between modalities after a negative test result are profoundly influenced by large variations in population event risk and a negative test result for all modalities conveys an excellent prognosis for patients with suspected or known CAD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Purpose: Radiopharmaceutical extravasation can potentially lead to severe soft tissue damage, but little is known about incidence, medical consequences, possible interventions, and effectiveness of these. The aims of this study are to estimate the incidence of extravasation of diagnostic and therapeutic radiopharmaceuticals, to evaluate medical consequences, and to evaluate medical treatment applied subsequently to those incidents., Methods: A sensitive and elaborate literature search was performed in Embase and PubMed using the keywords "misadministration", "extravasation", "paravascular infiltration", combined with "tracer", "radionuclide", "radiopharmaceutical", and a list of keywords referring to clinically used tracers (i.e. "Technetium-99m", "Yttrium-90"). Reported data on radiopharmaceutical extravasation and applied interventions was extracted and summarised., Results: Thirty-seven publications reported 3016 cases of diagnostic radiopharmaceutical extravasation, of which three cases reported symptoms after extravasation. Eight publications reported 10 cases of therapeutic tracer extravasation. The most severe symptom was ulceration. Thirty-four different intervention and prevention strategies were performed or proposed in literature., Conclusions: Extravasation of diagnostic radiopharmaceuticals is common. 99m Tc, 123 I, 18 F, and 68 Ga labelled tracers do not require specific intervention. Extravasation of therapeutic radiopharmaceuticals can give severe soft tissue lesions. Although not evidence based, surgical intervention should be considered. Furthermore, dispersive intervention, dosimetry and follow up is advised. Pharmaceutical intervention has no place yet in the immediate care of radiopharmaceutical extravasation.

Purpose: Amyloid-beta (Aβ) peptides are involved in the inflammatory pathology of atherosclerosis. 18 F-Florbetaben is a PET tracer for clinical imaging of cerebral Aβ plaques in Alzheimer's disease (AD). We sought to determine whether specific uptake of 18 F-florbetaben in the carotid arteries can be identified using a fully integrated hybrid PET/MRI system and whether this uptake is associated with clinical cardiovascular disease (CVD) risk factors., Methods: Carotid 18 F-florbetaben uptake was quantified as the mean of the maximum target-to-background ratio ( mean TBR max ) in 40 cognitively impaired subjects (age 68.2 ± 9.5 years) undergoing 18 F-florbetaben PET/MRI to diagnose AD. Associations between carotid 18 F-florbetaben uptake and several CVD risk factors were assessed by univariate analysis followed by a multivariate linear regression analysis. Furthermore, carotid 18 F-florbetaben uptake was compared between patients with and without a positive cerebral Aβ PET scan., Results: 18 F-Florbetaben uptake was clearly visualized in the carotid arteries. Values of mean TBR max corrected for the blood pool activity of the tracer showed specific 18 F-florbetaben uptake in the carotid wall. Male gender was associated with carotid 18 F-florbetaben uptake in the univariate analysis, and was found to be an independent predictor of 18 F-florbetaben uptake in the multivariate regression analysis (standardized regression coefficient β = 0.407, p = 0.009). Carotid 18 F-florbetaben mean TBR max in patients with a positive cerebral Aβ scan did not differ from that in patients without cerebral Aβ deposits., Conclusion: Specific 18 F-florbetaben uptake in human carotid arteries was detected. Male gender was identified as an independent clinical risk factor. Therefore, 18 F-florbetaben PET/MRI might provide new insights into the pathophysiological process in atherosclerosis.

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

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.

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.

Management of patients with acute chest pain remains challenging. Cardiac biomarker testing reduces the likelihood of erroneously discharging patients with acute myocardial infarction (AMI). Despite normal contemporary troponins, physicians have still been reluctant to discharge patients without additional testing. Nowadays, the extremely high negative predictive value of current high-sensitivity cardiac troponin (hs-cTn) assays challenges this need. However, the decreased specificity of hs-cTn assays to diagnose AMI poses a new problem as noncoronary diseases (eg, pulmonary embolism, myocarditis, cardiomyopathies, hypertension, renal failure, etc) may also cause elevated hs-cTn levels. Subjecting patients with noncoronary diseases to unnecessary pharmacological therapy or invasive procedures must be prevented. Attempts to improve the positive predictive value to diagnose AMI by defining higher initial cutoff values or dynamic changes over time inherently lower the sensitivity of troponin assays. In this review, we anticipate a potential changing role of noninvasive imaging from ruling out myocardial disease when troponin values are normal toward characterizing myocardial disease when hs-cTn values are (mildly) abnormal., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

Cardiovascular diseases are the leading cause of death not only in Europe but also in the rest of the World. Preventive measures, however, often fail and cardiovascular disease may manifest as an acute coronary syndrome, stroke or even sudden death after years of silent progression. Thus, there is a considerable need for innovative diagnostic and therapeutic approaches to improve the quality of care and limit the burden of cardiovascular diseases. During the past 10 years, several retrospective and prospective clinical studies have been published using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to quantify inflammation in atherosclerotic plaques. However, the current variety of imaging protocols used for vascular (arterial) imaging with FDG PET considerably limits the ability to compare results between studies and to build large multicentre imaging registries. Based on the existing literature and the experience of the Members of the European Association of Nuclear Medicine (EANM) Cardiovascular Committee, the objective of this position paper was to propose optimized and standardized protocols for imaging and interpretation of PET scans in atherosclerosis. These recommendations do not, however, replace the individual responsibility of healthcare professionals to make appropriate decisions in the circumstances of the individual study protocols used and the individual patient, in consultation with the patient and, where appropriate and necessary, the patient's guardian or carer. These recommendations suffer from the absence of conclusive evidence on many of the recommendations. Therefore, they are not intended and should not be used as "strict guidelines" but should, as already mentioned, provide a basis for standardized clinical atherosclerosis PET imaging protocols, which are subject to further and continuing evaluation and improvement. However, this EANM position paper might indeed be a first step towards "official" guidelines on atherosclerosis imaging with PET.

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 < 0.001]), but did not significantly change if calcification was present at baseline., 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., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

During the past years, non-neuronal vascular nicotinic acetylcholine receptors (nAChRs) increasingly have gained interest in cardiovascular research, as they are known to mediate the deleterious effects of nicotine and nitrosamines, components of tobacco smoke, on the vasculature. Because smoking is a major risk factor for the development of atherosclerosis, it is obvious that understanding the pathophysiologic role of nAChRs in the atherosclerotic disease process, as well as in the development of new diagnostic and therapeutic nAChR-related options, has become more important. Accordingly, we briefly summarize the pathophysiologic role of vascular nAChRs in the atherosclerotic disease process. We also provide an overview of currently available nAChR positron emission tomography (PET) tracers and their performance in the noninvasive imaging of vascular nAChRs, as well as potential nAChR PET tracers that might be an option for vascular nAChR PET imaging in the future.

Purpose: The objective of the study was to systematically assess aortic inflammation in patients with granulomatosis with polyangiitis (GPA) using (18)F-2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) positron emission tomography (PET)/CT., Methods: Aortic inflammation was studied in PET/CT scans obtained from 21 patients with GPA; 14 patients with sarcoidosis were included as disease controls, 7 patients with stage I or II head and neck carcinoma ascertained during routine clinical practice were used as healthy controls (HC) and 5 patients with large vessel vasculitis (LVV) were used as positive controls. Aortic (18)F-FDG uptake was expressed as the blood-normalized maximum standardized uptake value (SUVmax), known as the target to background ratio (mean TBRmax)., Results: The mean TBRmax (interquartile range) of the aorta in patients with GPA, sarcoidosis, HC and LVV were 1.75 (1.32-2.05), 1.62 (1.54-1.74), 1.29 (1.22-1.52) and 2.03 (1.67-2.45), respectively. The mean TBRmax was significantly higher in patients suffering from GPA or LVV compared to HC (p < 0.05 and p < 0.005, respectively) and tended to be higher in patients suffering from sarcoidosis, but this did not reach statistical significance (p = 0.098). The mean TBRmax of the most diseased segment was significantly higher compared to HC [1.57 (1.39-1.81)] in LVV patients [2.55 (2.22-2.82), p < 0.005], GPA patients [2.17 (1.89-2.83), p < 0.005] and patients suffering from sarcoidosis [2.04 (1.88-2.20), p < 0.05]. In GPA patients, the mean TBRmax of the aorta was significantly higher in patients with previous renal involvement [2.01 (1.69-2.53)] compared to patients without renal involvement in the past [1.60 (1.51-1.80), p < 0.05]. Interrater reproducibility with a second reader was high (all intraclass correlation coefficients >0.9)., Conclusion: Patients suffering from GPA show marked aortic FDG uptake.

In this study, we unravel a molecular imaging marker correlated with the known reduction of cardiovascular events (most commonly related to vulnerable plaques) in morbidly obese patients after bariatric surgery (BaS).We prospectively imaged 10 morbidly obese subjects with F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography before and 1 year after BaS. F-FDG uptake-which is enhanced in inflamed, atherosclerotic vessels and in metabolically active adipose tissues-was quantified in the carotids, pericardial adipose tissue (PAT), visceral adipose tissue (VAT), as well as brown adipose tissue (BAT). The degree of carotid inflammation was compared to lean and overweight controls.Carotid inflammation significantly declined leading to an F-FDG uptake comparable to the 2 control groups. Metabolic activity significantly decreased in PAT and VAT and increased in BAT.BaS leads to a normalization of carotid artery inflammation and a beneficial impact on the metabolic activity in PAT, VAT, and BAT that is related to the metabolic syndrome observed in this patient group.

Fever of unknown origin (FUO) represents a challenge in diagnosis and treatment. The role of 18Ffluorodeoxyglucose positron emission tomography (FDG-PET) / computed tomography (CT) in the differential diagnosis of this entity is presently well established. We report the case of a patient with infectious/inflammatory symptoms but no evident localization and subsequent relapse, in which PET/CT showed its ability to not only determine the exact localization of a thrombophlebitic focus as cause of FUO, but also to monitor and determine the success of treatment. After performing a FDG-PET/CT and detecting a thrombophlebitis in the brachiocephalic vein, low molecular heparins were introduced in the course of therapy. Soon (about 24 hours) thereafter, clinical symptoms significantly decreased and could no longer be observed. After continuing the antibiotic and anticoagulant therapy for 4 weeks, a follow-up PET/CT scan was performed. That scan no longer showed abnormal uptake in the previous intravascular localization. Consequently, we suggest that PET/CT is a diagnostic modality feasible to identify and monitor therapy response of intravascular thrombophlebitic foci.

Background: Fat 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 (18)FDG-PET-assessed inflammation of the aorta and the (visceral) fat, and evaluate its interrelations and differences in subjects with and without COPD., Methods: We retrospectively identified 42 patients (71% male, 48% current smokers, mean age 66.6 ± 8.3 years, mean BMI 25.1 ± 4.3 kg/m(2)), who underwent (18)F-FDG-PET/CT for suspected early stage bronchus carcinoma. COPD-diagnosis was based on spirometry and defined as FEV1/FVC < lower limit of normal. Inflammatory status of aortic and fat regions was defined as the average of obtained maximum target-to-background ratios (meanTBRmax). The TBR is the standardized uptake value (SUV) normalized to (18)F-FDG blood pool activity., Results: Compared to controls, patients with COPD (n = 19; 45%) had increased meanTBRmax of both the abdominal aorta (1.31 ± 0.14 vs. 1.49 ± 0.31; p = 0.02) and the abdominal visceral fat (0.28 ± 0.09 vs. 0.38 ± 0.18; p = 0.047), while inflammatory activity of the abdominal subcutaneous fat failed to show statistically significant differences (0.21 ± 0.09 vs. 0.24 ± 0.09; p = 0.345). In all patients, meanTBRmax of abdominal visceral fat was correlated with meanTBRmax of the abdominal aorta, independently of age and BMI (β = 0.590, p = 0.002)., Conclusion: Metabolic activity of the abdominal aorta and visceral fat is increased in COPD patients compared to peers. The degree of visceral fat metabolic activity is associated with aortic inflammation. More prospective research is warranted concerning the role of visceral fat in the development of vascular comorbidity in COPD., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: There is evidence that the link between obesity and cardiovascular disease might relate to inflammation in both fat tissue and the arterial wall. (18)F-FDG uptake on PET is a surrogate marker of vessel wall inflammation. The aim of the study was to measure FDG uptake in both regions using PET and identify links between adipose and arterial inflammation., Methods: Included in the study were 173 cardiovascular patients who were prospectively imaged with FDG PET/CT. Arterial FDG uptake was measured in the carotid arteries and ascending aorta. The same was done in fat tissue in the neck, the presternal region (both subcutaneous) and the pericardium. FDG uptake was quantified as average maximal target-to-background ratio (mean TBR max). Multivariate regression analyses were performed to identify significant associations between arterial and adipose tissue FDG uptake and clinical variables as given by the standardized correlation coefficient (β)., Results: FDG uptake values in all fat tissue regions were highly predictive of vascular FDG uptake in both the carotids (β 0.262, p < 0.0001, in the neck subcutaneous region) and aorta (β 0.22, p = 0.008, in the chest pericardial region; β 0.193, p = 0.019, in the chest subcutaneous region). Obesity was significantly associated with elevated FDG uptake in adipose tissue (β 0.470, p < 0.0001, in the neck subcutaneous region; β 0.619, p = 0.028, in the chest subcutaneous region; β 0.978, p = 0.035, in the chest pericardial region)., Conclusion: FDG uptake in diverse fat tissue regions was significantly associated with arterial FDG uptake, a reasonable surrogate of inflammation. Increasing body weight significantly predicted the level of fatty inflammation. FDG PET therefore provides imaging evidence of an inflammatory link between fat tissue and the vasculature in patients with cardiovascular disease.

Purpose: Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological (18)F-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, (18)F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to (18)F-FDG, other radiopharmaceuticals such as (99m)Tc-sestamibi, (123)I-metaiodobenzylguanidine (MIBG), (18)F-fluorodopa and (18)F-14(R,S)-[(18)F]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 < 0.05 in multivariable models were considered independently significant. Interleukin-6, systolic blood pressure and standard deviation of wall thickness (WT) at baseline were independently positively associated with 18-FDG uptake (mean of maximum [MeanMax] TBR change over 6 months). Mean of mean TBR, phospholipase A2, apolipoprotein A-I, and high-sensitivity C-reactive protein at baseline were independently negatively associated with MeanMax TBR change over 6 months. Mean WT and plasminogen activator inhibitor-1 (PAI-1) activity at baseline, and age, were independently associated with change in WA over 24 months. For TVA changes; mean WA and PAI-1 activity at baseline, age, and female gender were independent predictors. These findings may help determine patients most suitable for clinical trials employing plaque inflammation or burden changes as endpoints.

Purpose: (18)F-FDG PET is increasingly used for imaging of vessel wall inflammation. However, limited data are available on the impact of methodological variables, i.e. prescan fasting glucose, FDG circulation time and injected FDG dose, and of different FDG uptake parameters, in vascular FDG PET imaging., Methods: Included in the study were 195 patients who underwent vascular FDG PET/CT of the aorta and the carotids. Arterial standardized uptake values (meanSUVmax), target-to-background ratios (meanTBRmax) and FDG blood-pool activity in the superior vena cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake values classified according to the tertiles of prescan fasting glucose levels, the FDG circulation time, and the injected FDG dose were compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood-pool FDG uptake., Results: Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l, showing a favorable relationship between arterial and blood-pool FDG uptake. FDG circulation times showed negative associations with aortic meanSUVmax values as well as SVC and JV FDG blood-pool activity, but positive correlations with aortic and carotid meanTBRmax values. Prescan glucose levels were negatively associated with aortic and carotid meanTBRmax and carotid meanSUVmax values, but were positively correlated with SVC blood-pool uptake. The injected FDG dose failed to show any significant association with vascular FDG uptake., Conclusion: FDG circulation times and prescan blood glucose levels significantly affect FDG uptake in the aortic and carotid walls and may bias the results of image interpretation in patients undergoing vascular FDG PET/CT. The injected FDG dose was less critical. Therefore, circulation times of about 2.5 h and prescan glucose levels less than 7.0 mmol/l should be preferred in this setting.

Background and Purpose: Hallmarks of vulnerable atherosclerotic plaques are inflammation that can be assessed with 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography, and increased neovascularization that can be evaluated by dynamic contrast-enhanced-MRI. It remains unclear whether these parameters are correlated or represent independent imaging parameters. This study determines whether there is a correlation between inflammation and neovascularization in atherosclerotic carotid plaques., Methods: A total of 58 patients with transient ischemic attack or minor stroke in the carotid territory and ipsilateral carotid artery stenosis of 30% to 69% were included. All patients underwent positron emission tomography/computed tomography and dynamic contrast-enhanced-MRI of the carotid plaque. 18Fluorine-fluorodeoxyglucose standard uptake values with target/background ratio were determined. Neovascularization was quantified by the mean (leakage) volume transfer constant Ktrans. Spearman rank correlation coefficients between target/background ratio and Ktrans were calculated., Results: Images suitable for further analysis were obtained in 49 patients. A weak but significant positive correlation between target/background ratio and mean Ktrans (Spearman ρ=0.30 [P=0.035]) and 75th percentile Ktrans (Spearman ρ=0.29 [P=0.041]) was found., Conclusions: There is a weak but significant positive correlation between inflammation on positron emission tomography/computed tomography and neovascularization as assessed with dynamic contrast-enhanced-MRI. Future studies should investigate which imaging modality has the highest predictive value for recurrent stroke, as these are not interchangeable., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00451529.

Purpose: Inflammation and neovascularization in vulnerable atherosclerotic plaques are key features for severe clinical events. Dynamic contrast-enhanced (DCE) MRI and FDG PET are two noninvasive imaging techniques capable of quantifying plaque neovascularization and inflammatory infiltrate, respectively. However, their mutual role in defining plaque vulnerability and their possible overlap has not been thoroughly investigated. We studied the relationship between DCE-MRI and (18)F-FDG PET data from the carotid arteries of 40 subjects with coronary heart disease (CHD) or CHD risk equivalent, as a substudy of the dal-PLAQUE trial (NCT00655473)., Methods: The dal-PLAQUE trial was a multicenter study that evaluated dalcetrapib, a cholesteryl ester transfer protein modulator. Subjects underwent anatomical MRI, DCE-MRI and (18)F-FDG PET. Only baseline imaging and biomarker data (before randomization) from dal-PLAQUE were used as part of this substudy. Our primary goal was to evaluate the relationship between DCE-MRI and (18)F-FDG PET data. As secondary endpoints, we evaluated the relationship between (a) PET data and whole-vessel anatomical MRI data, and (b) DCE-MRI and matching anatomical MRI data. All correlations were estimated using a mixed linear model., Results: We found a significant inverse relationship between several perfusion indices by DCE-MRI and (18)F-FDG uptake by PET. Regarding our secondary endpoints, there was a significant relationship between plaque burden measured by anatomical MRI with several perfusion indices by DCE-MRI and (18)F-FDG uptake by PET. No relationship was found between plaque composition by anatomical MRI and DCE-MRI or (18)F-FDG PET metrics., Conclusion: In this study we observed a significant, weak inverse relationship between inflammation measured as (18)F-FDG uptake by PET and plaque perfusion by DCE-MRI. Our findings suggest that there may be a complex relationship between plaque inflammation and microvascularization during the different stages of plaque development. (18)F-FDG PET and DCE-MRI may have complementary roles in future clinical practice in identifying subjects at high risk of cardiovascular events.

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.

Objectives: The aim of this study was to noninvasively detect the anti-inflammatory properties of the novel liver X receptor agonist R211945., Background: R211945 induces reversal cholesterol transport and modulates inflammation in atherosclerotic plaques. We aimed to characterize with (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) and dynamic contrast-enhanced cardiac magnetic resonance (DCE-CMR) inflammation and neovascularization, respectively, in atherosclerotic plaques with R211945 treatment compared with atorvastatin treatment and a control., Methods: Twenty-one atherosclerotic New Zealand white rabbits were divided into 3 groups (control, R211945 [3 mg/kg orally], and atorvastatin [3 mg/kg orally] groups). All groups underwent (18)F-FDG-PET/CT and DCE-CMR at baseline and at 1 and 3 months after treatment initiation. Concomitantly, serum metabolic parameters and histology were assessed. For statistical analysis, continuous DCE-CMR and PET/CT outcomes were modeled as linear functions of time by using a linear mixed model, whereas the histological data, animal characteristics data, and nonlinear regression imaging data were analyzed with a 2-tailed Student t test., Results: (18)F-FDG-PET/CT detected a decrease in mean and maximum standard uptake values (SUV) over time in the R211945 group (both p = 0.001), indicating inflammation regression. The atorvastatin group displayed no significant change (p = 0.371 and p = 0.600, respectively), indicating no progression or regression. The control group demonstrated an increase in SUV (p = 0.01 and p = 0.04, respectively), indicating progression. There was a significant interaction between time and group for mean and maximum SUV (p = 0.0003 and p = 0.0016, respectively) . DCE-CMR detected a trend toward difference (p = 0.06) in the area under the curve in the atorvastatin group, suggesting a decrease in neovascularization. There was no significant interaction between time and group (p = 0.6350 and p = 0.8011, respectively). Macrophage and apolipoprotein B immunoreactivity decreased in the R211945 and atorvastatin groups (p < 0.0001 and p = 0.0004, respectively), and R211945 decreased oxidized phospholipid immunoreactivity (p = 0.02)., Conclusions: Noninvasive imaging with (18)F-FDG-PET/CT and DCE-CMR and histological analysis demonstrated significant anti-inflammatory effects of the LXR agonist R211945 compared with atorvastatin. The results suggest a possible role for LXR agonists in the treatment of atherosclerosis., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this feasibility study was to evaluate [(18)F]-2-Fluoro-A85380 for in vivo imaging of arterial nicotinic acetylcholine receptors (nAChRs) in humans. Furthermore, potentially different vascular uptake patterns of this new tracer were evaluated in healthy volunteers and in patients with neurodegenerative disorders., Background: [(18)F]-2-Fluoro-A85380 was developed for in vivo positron emission tomography (PET) imaging of nAChR subunits in the human brain. These nAChRs are also found in arteries and seem to mediate the deleterious effects of nicotine as a part of tobacco smoke in the vasculature. It has been previously shown that uptake patterns of the radiotracer in the brain differs in patients with neurodegenerative disorders compared with healthy controls., Methods: [(18)F]-2-Fluoro-A85380 uptake was quantified in the ascending and descending aorta, the aortic arch, and the carotids in 5 healthy volunteers and in 6 patients with either Parkinson's disease or multiple system atrophy, respectively, as the maximum target-to-background ratio. The maximal standardized uptake value values, the single hottest segment, and the percent active segments of the [(18)F]-2-Fluoro-A85380 uptake in the arteries were also assessed., Results: [(18)F]-2-Fluoro-A85380 uptake was clearly visualized and maximum target-to-background ratio uptake values corrected for the background activity of the tracer showed specific tracer uptake in the arterial walls. Significantly higher uptake values were found in the descending aorta. Comparison between volunteers and patients revealed significant differences, with lower [(18)F]-2-Fluoro-A85380 uptake in the patient group when comparing single arterial territories but not when all arterial territories were pooled together., Conclusions: [(18)F]-2-Fluoro-A85380 can provide specific information on the nAChR distribution in human arteries. Vascular nAChR density seems to be lower in patients with Parkinson's disease or multiple system atrophy. Once confirmed in larger study populations and in the experimental setting, this approach might provide insights into the pathogenic role of nAChRs in the human vasculature., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Unlabelled: This retrospective study compared the effects of single and multiple administrations of (186)Re-hydroxyethylidenediphosphonate ((186)Re-HEDP) on palliation and survival of prostate cancer patients presenting with more than 5 skeletal metastases., Methods: A total of 60 patients were divided into 3 groups. Group A (n = 19) consisted of patients who had received a single injection; group B (n = 19), patients who had 2 injections; and group C (n = 22), patients who had 3 or more successive injections. The (188)Re-HEDP was prepared using non-carrier-added (188)Re obtained from an in-house (188)W/(188)Re generator after dilution with carrier perrhenate. Patients' data available from the referring physicians-including prostate-specific antigen levels-were entered into a Windows-based matrix and analyzed using a statistical program. The Gleason scores were similar for all 3 groups., Results: Mean survival from the start of treatment was 4.50 ± 0.81 mo (95% confidence interval [CI], 2.92-6.08) for group A, 9.98 ± 2.21 mo (95% CI, 5.65-14.31) for group B, and 15.66 ± 3.23 (95% CI, 9.33-22.0) for group C. Although the 3 groups did not differ in Gleason score, the number of lost life-years was significantly lower in group C than in groups A and B. Pain palliation was achieved in 89.5% of group A, 94.7% of group B, and 90.9% of group C., Conclusion: Posttreatment overall survival could be improved from 4.50 to 15.66 mo by multiple-injection bone-targeted therapy with (188)Re-HEDP, when compared with a single injection. Significant pain palliation was common and independent of administration frequency.

Metaiodobenzylguanidine (MIBG) is a tracer that selectively targets neuroendocrine cells. On this basis, radiolabeled iodinated-MIBG (I-131-MIBG) has been introduced as a molecular nuclear therapy in the management of neuroendocrine tumors, including neuroblastoma, pheochromocytoma, paraganglioma, neuroendocrine carcinomas, and other rare neuroendocrine tumors. Extensive work has been addressed to develop I-131-MIBG therapy: doses, therapeutic schemes, and efficiency. In this paper, we present an overview on I-131-MIBG therapy, with main focus on different aspects how to perform this treatment., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: We investigated the prevalence and clinical risk factors of carotid vessel wall inflammation by means of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in a population consisting of coronary artery disease (CAD) patients., Background: The atherosclerotic disease process is characterized by infiltration and retention of oxidized lipids in the artery wall, triggering a disproportionate inflammatory response. Efforts have been made to use noninvasive imaging to quantify this inflammatory response in the vessel wall. Recently, carotid FDG-PET has been shown to reflect the metabolic rate of glucose, a process known to be enhanced in inflamed tissue., Methods: Carotid inflammation was quantified in 82 CAD patients (age 62 ± 10 years) as the maximum target-to-background ratio ((wholevessel)TBR(max)). Furthermore, we assessed the maximal standardized uptake value values ((wholevessel)SUV(max)), the single hottest segment (SHS), and the percent active segments (PAS) of the FDG uptake in the artery wall, measured by FDG-PET., Results: Whole-vessel TBR(max) >1.8 was present in 67%, >2.0 in 39%, >2.2 in 23%, and >2.4 in 12% of the population. Multiple linear regression analysis with backward elimination revealed that body mass index (BMI) ≥30 kg/m2 (p < 0.0001), age >65 years (p = 0.01), smoking (p = 0.02), and hypertension (p = 0.01) were associated with (wholevessel)TBR(max). The number of components of the metabolic syndrome was also associated with (wholevessel)TBR(max) (p = 0.02). In similar analyses, (wholevessel)SUV(max) was associated with BMI ≥30 kg/m2 (p < 0.0001), age >65 years (p = 0.004), male gender (p = 0.02), and hypertension (p = 0.04); SHS with BMI ≥30 kg/m2 (p < 0.0001), age >65 years (p = 0.02), smoking (p = 0.04), and hypertension (p = 0.05); PAS with BMI ≥30 kg/m2 (p = 0.001), smoking (p = 0.03), and hypertension (p = 0.01)., Conclusions: Carotid inflammation as revealed by FDG-PET is highly prevalent in the CAD population and is associated with obesity, age over 65 years, history of hypertension, smoking, and male gender. Artery wall FDG uptake increased when components of the metabolic syndrome clustered., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The aim of the present study was to assess the impact of female gender on the extent of myocardial perfusion defects as revealed by (99m)Tc-sestamibi myocardial perfusion scintigraphy (MPS) and on emerging cardiac events (CE) in patients aged ≥ 70 years., Patients and Methods: 86 patients aged ≥ 70 years with known or suspected CAD undergoing MPS (74.4 ± 3.2 years; women: n = 46; 53.5%) were included in this study. Semiquantitative analysis of MPS was performed and summed stress (SSS), summed difference (SDS), and summed rest scores (SRS) were calculated. Emerging CE comprised myocardial revascularization and -infarction and cardiac-related death. Multivariate regression analysis was performed to assess the independent prognostic impact of several patient related variables on MPS results. Kaplan-Meier- and log rank analyses were calculated for assessment of CE free survival as related to gender., Results: Normal SSS (87.0% vs. 27.5%; p < 0.0001), SDS (80.4% vs. 27.5%; p < 0.0001), and SRS (97.8% vs. 82.5%; p = 0.023) were significantly more often found in women, whereas incidence of mildly and severely impaired SSS (6.5% vs. 35%; p = 0.001 and 2.2% vs. 25%; p = 0.002, respectively) and SDS (15.2% vs. 52.5%; p < 0.0001 and 2.2% vs. 17.5%; p = 0.023, respectively) were significantly higher in men. Multivariate logistic regression analysis revealed female gender as an independent predictor of normal SSS (odds ratio/OR: 17.6) and SDS (OR: 53.3). Female gender was associated with a significant higher cardiac-death free survival compared to male patients (p = 0.031)., Conclusion: Female gender is independently associated with a significantly lower degree of pathological MPS results and a higher cardiac-death free survival in elderly patients.

Malignant fibrous histiocytomas are rare soft-tissue sarcomas of uncertain histogenesis but represent the most common soft-tissue sarcomas in adults. In this report of a 70-year-old male patient suffering from this rare malignant disease, we describe the diagnostic benefits of combined functional and morphological imaging as realized in positron emission tomography and computed tomography, helping to avoid invasive diagnostic methods and, most importantly, harmful and quality-of-life-reducing, oncologically ineffective therapies.

The diagnostic accuracy of 18F-FDG-PET (fluoro-2-deoxyglucose-positron emission tomography) remains questionable for primary hepatocellular carcinoma (HCC) but seems to be more promising for restaging and therapy control. Yet, there are no data on FDG-PET in 131I-lipiodol treatment for primary liver cancer. The aim of this study was to relate baseline FDG-PET findings to histologic data and to assess, for the first time, the role of repetitive FDG-PET imaging for follow-up of 131I-lipiodol treatment. Eighteen (18) patients (16 HCC, 2 cholangiocellular carcinoma; CCC) with 36 treatment courses (up to four per patient) had 35 PET exams, including 18 post-treatment follow-up scans in 10 patients (up to three per patient, one without baseline PET; n = 17). Histopathologic results were available in 15 patients. PET results were retrospectively related to histopathologic type, grading, presence of cirrhosis, and tumor size at baseline and compared with computed tomography (CT) during follow-up. Prior to 131I-lipiodol treatment, 8 patients were PET positive and 9 PET negative. Most of the large HCCs were PET positive and most small tumors PET negative (p < 0.05), despite an overlap below 11 cm. There was no identifiable correlation between PET results and degree of tumor differentiation. Overall, 9 of 10 patients with 17 of 18 follow-up scans showed concordant results with CT. The one discrepant case became PET negative after the first treatment course, despite CT-proven tumor growth (false negative). Patient management was not changed due to PET results. In conclusion, large HCCs were significantly more often PET positive, but there was no correlation with the degree of differentiation. Follow-up PET may be useful if the tumor is first demonstrated to be FDG positive.

There is little data regarding the impact of subclinical hyperthyroidism on coagulation metabolism in patients undergoing systemic anticoagulation therapy with coumarin derivates. In this retrospective analysis we studied 233 patients with benign thyroid disorders receiving therapeutic iodine-131, as well as concomitant systemic anticoagulation therapy (subclinical hyperthyroidism: n = 178; overt hyperthyroidism: n = 15; euthyroidism: n = 40). Multivariate regression analyses were performed in the total study population as well as in the subgroup of patients with subclinical hyperthyroidism to identify the possible impact of several variables on anticoagulation therapy, large enough to push the International Normalized Ratio (INR) level out of the therapeutic range (INR <2.0 or >3.0). Therapy with antibiotics or nitrates was significantly associated with INR-values >3.0 in the total population, while ACE inhibitors were associated with lower incidence of INR-values <2.0. In patients with subclinical hyperthyroidism, therapy with antibiotics was predictive of INR-values >3.0, whereas therapy with thyroid suppressive drugs or TSH-values <0.1 mU/l was associated with INR-values <2.0. Moreover, in a subgroup of 40 patients with the positive history of both subclinical hyperthyroidism and euthyroidism intraindividual comparison with regard to the possible impact on anticoagulation therapy was performed which failed to show any significant differences in INR-values between the two thyroid metabolic conditions. In conclusion, subclinical hyperthyroidism seems to have no significant impact on coagulation metabolism in patients receiving anticoagulation therapy.

Purpose: Recently published data indicated (18)F-fluorocholine to be feasible for imaging vulnerable atherosclerotic plaques in an animal model., Methods: Five patients undergoing whole-body (18)F-fluoromethylcholine-((18)F-FMCH-) PET/CT for imaging of prostate cancer disease were retrospectively evaluated. Whole-body PET scans were started immediately after i.v. injection of (18)F-FMCH. About 5-15 min after tracer injection, acquisition of scans of the pelvis and abdomen was performed. PET, CT, and PET/CT slices were generated for review and visual analyses of the abdominal aorta and the common iliac arteries were performed. Vascular findings in examined arteries and surrounding structures due to artifacts were excluded from further analysis. The lower threshold of (18)F-FMCH uptake was set above the background activity within the examined vessels. Morphological classification of vessel wall alterations (WA) included structural wall alterations without additional calcification (SWA), structural wall alterations associated with calcifications (SWC), and solely calcified lesions (CL). They were correlated with (18)F-FMCH uptake qualified as present and vice versa., Results: A total of 31 WA were identified. Positive (18)F-FMCH uptake was found in 14 lesions (SWA: n = 5; SWC: n = 9). Sixteen of 17 (18)F-FMCH negative lesions were identified as CL without additional structural vessel wall alteration. One SWA did not show any (18)F-FMCH accumulation. None of the CLs as well as unaltered parts of the vessel wall showed (18)F-FMCH uptake., Conclusions: Our initial data in five patients with a total of 31 vessel wall alterations show promising results indicating for the first time the feasibility of (18)F-FMCH for in vivo imaging of structural WA in humans.

Papillary carcinoma is the most common malignancy of the thyroid gland with initial lymphogenic metastatic spread in many cases. Hematogenous spread may affect the lung, bone and brain. We present a case of hematogenous metastases of papillary thyroid carcinoma both in the choroid and the skin, which are reported in the literature to be rare sites of metastases in primary differentiated thyroid carcinoma. This finding is even more remarkable, as the reported patient presented without any other disseminated hematogenous metastases at the time of diagnosis of both of these metastases. With this background, papillary carcinoma of the thyroid should be considered in the differential diagnosis of choroidal or skin metastasis of unknown origin.

Background: As single-head data acquisition for thallium-201 myocardial SPECT is a frequently used method mainly in the outpatient medical care as well as in smaller hospitals, comparison to dual-head data collection is a still discussed issue mainly with regard to quality control and -assurance., Methods: A total of 1334 patients undergoing thallium-201 myocardial SPECT for diagnosis of myocardial ischemia and/or viability have been retrospectively analyzed. In 554 patients, a single-head gamma camera (360 degrees rotation) has been applied, whereas a dual-head gamma camera (180 degrees rotation) has been used in 780 patients. Four hundred twenty-six patients received both myocardial SPECT as well as coronary angiography. The diagnostic value of both applied acquisition techniques has been analyzed., Results: Regarding myocardial viability, positive predictive value for the diagnosis of myocardial scar tissue was significantly higher for dual-head- as compared to single-head acquisition. Among the 426 patients undergoing diagnosis of myocardial ischemia, significant differences have only been found with regard to specificity being higher in the single-head acquisition. Diagnosis of myocardial ischemia related to a distinct myocardial perfusion region showed a significantly higher sensitivity of dual-head acquisition for the left anterior descending perfusion area, whereas specificity was significantly higher for single-head acquisition., Conclusions: Our results indicate a beneficial effect of dual-head data collection with regard to sensitivity of the diagnosis of myocardial ischemia. In contrast, single-head data acquisition was superior with regard to specificity. However, it is justified to preferably apply dual-head data collection in clinical routine due to the shorter acquisition time leading to an evident time benefit of this acquisition technique.

History and Admission Findings: A 41-year-old woman presented with hyperhydrosis, tremor, restlessness, sleeplessness and diarrhea. She had a tachycardia and later she developed soreness of her conjunctives. A tender goitre could be palpated., Investigations: Laboratory results showed thryeotoxicosis and later elevated TRAK. Ultrasound revealed a thyroid nodule. Scintigraphic uptake was generally elevated. Graves disease was diagnosed., Treatment and Course: After 12 months of thyreostatic medication recurrence occurred and a thyroidectomy was performed. Histologically a papillary cancer was found and postoperative radioiodinetherapy was added., Conclusion: Due to leading symptoms of thyreotoxicosis the thyroid nodule has preoperatively not been paid enough attention to. A pathophysiologic association of Graves disease and differentiated thyroid cancer is controversely discussed but seems possible considering present literature data. Scintigraphically "cold" nodules in graves disease, as in simple nodular goitre, have a higher probability of malignancy.

Objective: 99mTc-tetrofosmin and 99mTc-sestamibi are approved tracers for myocardial perfusion studies. Recently, a 99mTc-MIBI preparation from a different manufacturer (99mTc-cardiospect-MIBI) has been introduced to the market. Therefore, the aim of this study was the evaluation of 99mTc-tetrofosmin as well as of two different 99mTc-labeled MIBI tracers with regard to differences in imaging quality under resting conditions., Methods: Sixty patients (mean age 63.8 years +/- 1.25) with known or suspected coronary artery disease but without evidence of rest-ischemia were included. Twenty patients in each group were examined by a two-day-rest-stress protocol using the three 99mTc-labeled tracers. Visual analysis of all images was performed by two experienced physicians blinded with regard to the applied tracer. Regions of interest (ROI) were defined over the heart, lung and whole body only in the rest imaging in order to calculate heart-to-lung, lung-to-whole body-, and heart-to-whole body-ratios., Results: The heart-to-lung ratio was statistically significant higher for 99mTc-cardiospect-MIBI as compared to 99mTc-sestamibi as well as to 99mTc-tetrofosmin. Furthermore, a significantly higher heart-to-lung ratio was found for 99mTc-sestamibi as compared to 99mTc-tetrofosmin. The heart-to-whole body-ratio and the lung-to-whole body-ratio were equivalent between all tracers. Visual analysis revealed only slight differences regarding image quality between all tracers., Conclusions: ROI analysis surprisingly revealed a significant higher myocardial uptake and consequently a higher heart-to-lung ratio for 99mTc-cardiospect-MIBI. Whether this leads to a better visual image quality has to be evaluated in future studies with larger study populations as well as semiquantitative segmental analysis of the myocardial perfusion images.

Unlabelled: Major depression (MD) is the most frequent psychiatric disorder with a predicted increase within the next decade. The understanding of the neurobiologic basis of its cause, antidepressive treatment effects, and identification of treatment outcome predictors is of crucial importance to warrant efficient medical care. The aim of our study was to investigate differences of regional cerebral blood flow (rCBF) in MD between responders and nonresponders in the beginning and differences during the course of treatment., Methods: 99mTc-Labeled d,l-hexamethylpropyleneamine oxime brain scans under resting conditions were performed on 65 patients with MD. All patients were treated with citalopram as an antidepressive monotherapy. SPECT scans were performed 2 times, at the beginning (t1) and after 4 wk of medication (t2). Voxel-by-voxel analyses were performed using SPM. Unpaired t test, paired t test, and multigroup analysis were used on a significance threshold of P < 0.005 (uncorrected) to identify significant differences in rCBF between responders and nonresponders at t1, within both groups over time of treatment (t2-t1), as well as a group x time interactions., Results: Thirty-five patients responded after 4 wk of treatment. Distinct differences between responders and nonresponders were found at the beginning of treatment and also relating to changes in rCBF during treatment. Responders showed a higher posterior cingulate activity at t1. Furthermore, an opposite direction of rCBF changes during treatment could be observed in this area., Conclusion: The differences in rCBF in responders and nonresponders in the posterior cingulate at t1 and the opposite directed changes in rCBF in both groups during treatment in this region suggest that the posterior cingulate function plays a key role in the pathophysiology of depression and may have a predictive value for antidepressive treatment outcome.

Nicotinic acetylcholine receptors (nAChR) are involved in many physiological functions and appear to be affected in neurodegenerative diseases like Alzheimer's disease and Parkinson's disease (PD). Here, we describe the in vitro evaluation of nAChRs in PD with 2-[18F]F-A85380, a ligand with high affinity to the beta2 nAChR subunit. Autoradiography with 2-[18F]F-A85380 in untreated rat brain corresponded to the known distribution of alpha4beta2 nAChRs with high uptake in the thalamus, moderate uptake in the striatum and cortex and low uptake in the cerebellum (47%, 43% and 19% of the thalamus, respectively). The localization of alpha4beta2 nAChRs in the striatum was investigated in rodents with unilateral lesion of the substantia nigra. 2-[18F]F-A85380 binding was significantly reduced in the striatum ipsilateral to the lesion side (to 64% of the contralateral side), indicating that a fraction of alpha4beta2 nAChRs is located on dopaminergic terminals, whereas another fraction resides on striatal interneurons or cortical afferents. Similarly, in human brain sections of PD patients, 2-[18F]F-A85380 uptake was significantly reduced not only in the caudate and putamen but also in the thalamus (approximately 30% of the binding of control brain in all three regions); within the striatum, nAChRs in the putamen were significantly more severely affected as in the caudate. The observed pattern of alpha4beta2* nAChR loss demonstrates the potential of 2-[18F]F-A85380 for further investigations of this positron emission tomography ligand for in vivo studies of alpha4beta2* nAChRs in PD.

Unlabelled: The aim of this study was to investigate the diagnostic accuracy and impact on patient management of the new integrated PET/CT modality in patients with suspected iodine-negative, differentiated thyroid carcinoma (DTC)., Methods: Forty patients with DTC and a suggestion of iodine-negative tumor tissue underwent PET/CT examination (370 MBq (18)F-FDG, coregistered PET/CT whole-body images). As the first step of analysis, PET and CT images were scored blindly and independently by 2 nuclear medicine physicians and 2 radiologists. A 5-point scale was used. The second step consisted of a consensus reading, during which a virtual side-by-side fusion of PET and CT images was initially evaluated and afterward the "real" fusion (i.e., coregistered) PET/CT images were also scored with the same 5-point scale. The imaging results were compared with histopathologic findings and the course of disease during further follow-up examinations., Results: One hundred twenty-seven lesions in 40 patients were evaluated. Diagnostic accuracy was 93% and 78% for PET/CT and PET, respectively (P = 0.049, per-patient analysis). In 17 (74%) of 23 patients with suspicious (18)F-FDG foci, integrated PET/CT added relevant information to the side-by-side interpretation of PET and CT images by precisely localizing the lesion(s). In tumor-positive PET patients, PET/CT fusion by coregistration led to a change of therapy in 10 (48%) patients. Futile surgery was prevented in an additional 3 patients., Conclusion: Integrated PET/CT is able to improve diagnostic accuracy in a therapeutically relevant way in patients with iodine-negative DTC. By precisely localizing tumor tissue, image fusion by integrated PET/CT is clearly superior to side-by-side interpretation of PET and CT images.