Aortic Uptake Research Articles

18 F]-Fludarabine Positron Emission Tomography in Chronic Lymphocytic Leukemia Patients: Results of a Phase I Study

Introduction. [18 F]-Fludarabine is a promising novel positron emission tomography (PET) radiotracer for lymphoid malignancies. The rationale supporting its development is the high selectivity of fludarabine uptake within lymphoid cells irrespective of their cycle activity, and the fluorine atom within the drug, which replaced by a [18 F] confers the positron-emitter property. Pre-clinical studies with [18 F]-fludarabine (Dhilly M et al, Mol Imaging Biol 2014,16:118-26; Hovhannisyan N et al, EJNMMI Res 2015,5:23) showed a marked tumor uptake in lymphoma-bearing mice. The aim of this study was to describe anatomical sites with abnormal [18 F]-fludarabine uptake in patients with B-cell chronic lymphocytic leukemia (B-CLL), in whom [18 F]-FDG PET imaging appears to be less informative than in other lymphoid malignancies. This study was designed as a clinical proof of concept.Methods. [18 F]-Fludarabine was produced according to a method already described (Guillouet S et al, Mol Imaging Biol 2014,16:28-35). [18 F]-Fludarabine PET/CT (Discovery RX VCT 64, GE Healthcare) was performed in 5 patients (51-70 years old) with a diagnosis of B-CLL (according to current recommendations), without suspicion of Richter's syndrome. Successive partial body scans (skull vertex to mid-thigh) were acquired for 250 min after intravenous injection of [18 F]-fludarabine with an activity of 4MBq/kg. PET images were analyzed by drawing volumes of interest (VOI) over the uptake sites on a late scan and projected onto all co-registered scans of the same subject. The intensity of tracer uptake was evaluated with the maximum standardized uptake value (SUVmax). The images of [18 F]-fludarabine PET/CT were visually compared with conventional modalities (high-resolution CT) and [18 F]-FDG PET in one patient.Results. No adverse event was recorded during and after the procedure. In the 5 patients studied, the uptake of [18 F]-fludarabine coincides with sites expected to be involved following conventional clinical and CT scan staging (i.e. lymph nodes, spleen, tonsils). Additionally, [18 F]-fludarabine PET/CT displayed a significant uptake in hematopoietic bone marrow, and unexpected uptake in the medulla of some bones (femur, humerus, sphenoid, calvarium), and in Peyer's patches. SUVmax were significantly greater in involved sites in comparison with normal tissues or organs (Figure 1). Within the involved sites, [18 F]-fludarabine demonstrated a wide range of uptake which would indicate heterogeneity and differing micro-environments. For instance, the most active sites of the case illustrated in Figure 1 (scan period 30-50 min) are lymph nodes (SUVmax 7.4), spleen (SUVmax 6.3) and bone marrow (SUVmax 3.8) with aortic uptake (SUVmax 1.5) as background level.Conclusion. These preliminary results showed a clear specificity of this novel radiotracer for lymphoid tissues. [18 F]-Fludarabine PET/CT appears to be a promising tool for the diagnosis and follow-up of B-CLL. These scans indicate variable activity within proliferation sites, information otherwise not accessible by current non-invasive procedures. Further studies for a more accurate comparison with [18 F]-FDG PET, evaluation of response during and after treatment and correlation with B-CLL prognostic criteria are underway. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

(18)F-FDG PET scanning of abdominal aortic aneurysms and correlation with molecular characteristics: a systematic review.

PurposeThe purpose of this study is to give an overview of studies investigating the role of fludeoxyglucose F18 (18F-FDG) positron emission tomography (PET) scanning in patients with aortic aneurysms with a focus on molecular characteristics of the aneurysm wall.MethodsMEDLINE, EMBASE, and the Cochrane database were searched for relevant articles. After inclusion and exclusion, we selected 18 relevant articles reporting on 18F-FDG PET scanning of aortic aneurysms.ResultsThe sample size of studies is limited, and there are no standardized imaging protocols and quantification methods. 18F-FDG PET scanning was shown to display molecular characteristics of the aortic wall. Different studies showed contradictory findings of aortic 18F-FDG uptake in aneurysm patients compared to controls.ConclusionsNon-invasively determining molecular characteristics of aortic wall weakening might lead to better rupture and growth prediction. This might influence the decision of the surgeon between conservative and surgical treatment of aneurysms. To date, there is conflicted evidence regarding the use of 18F-FDG PET scanning to predict aneurysm rupture and growth. The role of 18F-FDG PET scanning in rupture risk prediction needs to be further investigated, and standardized imaging protocols and quantification methods need to be implemented.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-015-0153-8) contains supplementary material, which is available to authorized users.

Evaluation of aortic 18F-NaF tracer uptake detected using PET/CT in predicting aortic calcification over a 4-year follow-up period

Evaluation of aortic 18F-NaF tracer uptake detected using PET/CT in predicting aortic calcification over a 4-year follow-up period

Abstract 15567: Increased Visceral Fat Volume is Associated With Aortic Inflammation and Cardiovascular Events

Introduction: While the relationship between obesity and cardiovascular disease (CVD) is well-established, mechanisms underlying this relationship are not well elucidated. Hypothesis: Our hypothesis is that visceral adipose tissue (VAT) volume, aortic inflammation and the risk of subsequent cardiovascular events are linked together. Methods: Individuals who underwent 18F-FDG PET/CT imaging were included. VAT volume, subcutaneous adipose tissue (SAT) volume and aortic FDG uptake were measured while blinded to clinical data. Cardiovascular events were adjudicated by independent cardiologists. Thereafter, the relationship between VAT volume and aortic FDG activity and cardiovascular events was evaluated using Cox proportional hazard models. Results: The final analysis included 415 patients with a median age of 55 (P25-P75: 45-65) years and a median BMI of 26.4 (P25- P75: 23.4-30.9) kg/m2. VAT and SAT volume were significantly higher in obese individuals. 32 subjects experienced cardiovascular event during a median follow-up of 4 years. Cox proportional hazard models showed that VAT volume was a associated with cardiovascular events (hazard ratio, HR (95% CI): 1.15 (1.06-1.25, p<0.001). This remained significant after correcting for age, BMI and aortic TBR (p<0.05). SAT was not predictive of cardiovascular events. VAT volume was associated with arterial inflammation (r=0.29, p<0.001, Figure 1). The combination of high aortic inflammation and high VAT volume was associated with significant worse survival (p<0.05). Conclusions: We observed that VAT volume is a predictor of subsequent cardiovascular events. Moreover, our results indicate a link between visceral adipose tissue volume and arterial inflammation, which may explain some of VAT's association with cardiovascular events.

Abstract 13271: Aortic Inflammation Continues in Patients With A History of Kawasaki Disease and Persistent Arterial Aneurysms

Introduction: Kawasaki disease (KD) is well known vasculitis that primarily affects small to middle sized arteries such as coronary arteries and/or peripheral arteries. However, little evidence showed inflammation of large vasculature such as the aorta in patients with KD. Measurements of 18F-fluorodeoxyglucose (FDG) uptake evaluated by positron emission tomography (PET) and X-ray computed tomography (CT) could be useful to identify inflammatory activity of the vessel wall. Hypothesis: We hypothesized that aortic inflammation continues long after KD. Methods: FDG-PET/CT was performed in 19 patients with a history of KD. Of 19 patients, 11 patients still had persistent coronary and/or systemic vascular aneurysms (KD-An) and the remaining 8 revealed regression of arterial aneurysms (KD-Reg). Patients suffered from KD at 2.8 ± 3.2 years old and underwent FDG-PET at 22.2 ± 8.0 years old. FDG-PET was also performed in 5 control with age 14.1 ± 2.6 years old. Vascular inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio (TBR). Also demographic and laboratory data were collected. Results: Aortic FDG uptake was distinctly intense in patients with a history of KD and persistent vascular aneurysms. The Aortic TBR was significantly higher in KD-An (1.50 ± 0.30) than KD-Reg (1.11 ± 0.13, p = 0.004) or controls (1.03 ± 0.25, p=0.003). Although Control was significantly younger and had significantly lower body mass index, there was no significant correlation between these values and TBR. Also there was no significant difference in laboratory data including lipid profiles and glycemic status among 3 groups. Conclusions: Vascular inflammation of the aortic wall continues long after KD with persistent arterial aneurysms.

Organic cation transporter 3 contributes to norepinephrine uptake into perivascular adipose tissue.

Perivascular adipose tissue (PVAT) reduces vasoconstriction to norepinephrine (NE). A mechanism by which PVAT could function to reduce vascular contraction is by decreasing the amount of NE to which the vessel is exposed. PVATs from male Sprague-Dawley rats were used to test the hypothesis that PVAT has a NE uptake mechanism. NE was detected by HPLC in mesenteric PVAT and isolated adipocytes. Uptake of NE (10 μM) in mesenteric PVAT was reduced by the NE transporter (NET) inhibitor nisoxetine (1 μM, 73.68 ± 7.62%, all values reported as percentages of vehicle), the 5-hydroxytryptamine transporter (SERT) inhibitor citalopram (100 nM) with the organic cation transporter 3 (OCT3) inhibitor corticosterone (100 μM, 56.18 ± 5.21%), and the NET inhibitor desipramine (10 μM) with corticosterone (100 μM, 61.18 ± 6.82%). Aortic PVAT NE uptake was reduced by corticosterone (100 μM, 53.01 ± 10.96%). Confocal imaging of mesenteric PVAT stained with 4-[4-(dimethylamino)-styrl]-N-methylpyridinium iodide (ASP(+)), a fluorescent substrate of cationic transporters, detected ASP(+) uptake into adipocytes. ASP(+) (2 μM) uptake was reduced by citalopram (100 nM, 66.68 ± 6.43%), corticosterone (100 μM, 43.49 ± 10.17%), nisoxetine (100 nM, 84.12 ± 4.24%), citalopram with corticosterone (100 nM and 100 μM, respectively, 35.75 ± 4.21%), and desipramine with corticosterone (10 and 100 μM, respectively, 50.47 ± 5.78%). NET protein was not detected in mesenteric PVAT adipocytes. Expression of Slc22a3 (OCT3 gene) mRNA and protein in PVAT adipocytes was detected by RT-PCR and immunocytochemistry, respectively. These end points support the presence of a transporter-mediated NE uptake system within PVAT with a potential mediator being OCT3.

YIA4 The Novel Alpha-V Beta-3 Integrin Positron Emission Tomography Radiotracer 18F-Fluciclatide is a Marker of Aortic Atherosclerosis Activity

<h3>Introduction</h3> Intra-plaque angiogenesis and inflammation are key promoters of plaque vulnerability. Angiogenic endothelial cells and macrophages express the integrin α_vβ₃. The novel RGD-based radiotracer 18F-Fluciclatide has high affinity for α_vβ₃ integrin and therefore may act as a surrogate marker of the unstable atherosclerotic plaque. <h3>Methods</h3> Forty-six subjects with a mixture of ischaemic heart disease and aortic stenosis, including 9 healthy subjects underwent CT-coronary angiography (CTCA) and combined PET/CT imaging of the thorax 40 min after the administration of 226 ± 13 mBq 18F-fluciclatide. Regions of interest were drawn around the thoracic aorta using serial axial slices on fused PET/CT images. 18F-Fluciclatide uptake in these regions was normalised for blood-pool activity in the superior vena cava using tissue to background ratio [TBR]. Reproducibility of this technique was assessed on 10 image-sets by two observers. Quantification and analysis of descending thoracic aortic atheroma on CTCA was performed using plaque analysis software. <h3>Results</h3> There was a close correlation between 18F-fluciclatide uptake and the extent of atherosclerosis within the aorta on CTCA, as measured by wall thickness (r = 0.62 [0.31–0.81], p= &lt;0.001] and total plaque burden (r = 0.60 [0.27–0.80], p = 0.001). Furthermore, aortic 18F-fluciclatide uptake (expressed as mean TBR_max) correlated with total aortic calcium score (AU) (r = 0.36 [0.05–0.60], p = 0.02) and was significantly greater in subjects with ischaemic heart disease (1.34 ± 0.03 vs 1.25 ± 0.03; p = 0.02) and hypercholesterolaemia (1.35 ± 0.03 vs 1.25 ± 0.03; p = 0.01). There were no significant age (r = 0.20(–0.12–0.47), p = 0.21) or sex related differences (1.34 ± 0.05 vs 1.29 ± 0.02, p = 0.24) and reproducibility analysis showed no fixed or proportional bias (0.07[–0.13–0.27]) with excellent intra-class correlation (0.98[0.92–1.0]). <h3>Conclusion</h3> The quantification of α_vβ₃ integrin expression within the aorta using 18F-fluciclatide is a highly reproducible marker of atherosclerotic burden. This supports further work in establishing its role in the assessment of the unstable plaque.

Aortic ¹⁸F-FDG uptake in patients suffering from granulomatosis with polyangiitis.

PurposeThe objective of the study was to systematically assess aortic inflammation in patients with granulomatosis with polyangiitis (GPA) using 18F-2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET)/CT.MethodsAortic 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 18F-FDG uptake was expressed as the blood-normalized maximum standardized uptake value (SUVmax), known as the target to background ratio (mean TBRmax).ResultsThe 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).ConclusionPatients suffering from GPA show marked aortic FDG uptake.Electronic supplementary materialThe online version of this article (doi:10.1007/s00259-015-3081-y) contains supplementary material, which is available to authorized users.

Abstract 330: Ezetimibe Prevents Atherogenesis Through Increased Catabolism and Fecal Excretion of LDL-cholesterol and Reduced Atherosclerotic Plaque Inflammation in Apolipoprotein E Knock-out Mice Fed a Paigen Diet

Background: Intestinal cholesterol absorption inhibitor ezetimibe (EZE) added to a statin therapy has demonstrated benefits in the IMPROVE-IT trial by further reducing LDL-cholesterol levels than statin therapy alone. We investigated the mechanisms by which EZE could contribute to cardiovascular events reduction in apolipoprotein E knock-out (apoE ko) mice. Methods: ApoE ko mice were fed a Paigen diet without (control) or with EZE (7mg/kg/day) for 6 weeks. To evaluate the effects of EZE on LDL-cholesterol metabolism and excretion, a first set of mice was injected intravenously with 3 H-cholesteryl oleate labeled human LDL. A second set of mice was used for in vivo SPECT/CT imaging of 99m Tc-cAbVCAM1-5, a single domain antibody directed against the Vascular Cell Adhesion Molecule-1 (VCAM-1), which was used as a marker of inflamed atherosclerotic plaques. The same mice were sacrificed for autoradiography and histology of aortic atherosclerotic plaques. Results: Compared with control, EZE treatment for 6 weeks induced a significant 41% and 65% reduction in plasma total cholesterol levels and atherosclerotic plaque area, respectively. After injection of 3 H-cholesteryl oleate labeled human LDL, mice treated with EZE showed a 173% higher LDL-cholesteryl ester catabolism (p&lt;0.001 vs. control). At time 96 hours after radiolabeled LDL injection, 3 H-tracer hepatic recovery was reduced by 61% with EZE (p&lt;0.001). Meanwhile, LDL-derived 3 H-tracer excretion in the feces was increased by 107% in the fecal cholesterol fraction (p&lt;0.001). Similar trends were observed for hepatic cholesterol levels and fecal cholesterol mass excretion, with a 75% reduction and 99% increase with EZE, respectively (both p&lt;0.001). After intravenous injection of 99m Tc-cAbVCAM1-5, mice treated with EZE also showed a significant 52% reduction in aortic uptake, which was confirmed by significant reduction in tracer uptake in ex vivo biodistribution and autoradiography analysis. Conclusion: EZE promotes anti-atherosclerotic effects through increased LDL-cholesterol catabolism and LDL-derived cholesterol fecal excretion, and reduced inflamed atherosclerotic plaques. These mechanisms may contribute to the benefits of adding EZE to a statin therapy.

(Tissue PET) Vascular metabolic imaging and peripheral plasma biomarkers in the evolution of chronic aortic dissections.

Despite adequate medical management, dissection of the descending aorta (type B) may develop complications, including aneurysmal progression and eventually rupture. Partial false lumen thrombosis has been identified as a marker of adverse evolution in chronic dissection. The aim of this study was to test the ability of complementary information, provided by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) and peripheral biomarkers, to add pathophysiological significance and a prognostic value to morphological data. We explored serial aortic (18)F-FDG uptake by PET/CT imaging and plasma biomarkers in a series of 23 patients with type B dissection to predict complications from initial data and to investigate potential associations with aneurysmal expansion during follow-up. Complications occurred in 17 patients. Acute initial characteristics associated with complications were male gender (P = 0.021), arterial hypertension (P = 0.040), aortic dissection diameter (P = 0.0086), partial thrombosis of the false channel (P = 0.0046), and enhanced focal (18)F-FDG uptake (P = 0.045). During follow-up (mean 16.7 ± 8.0 months), aneurysmal expansion was associated with false lumen morphology (P< 0.0001), quantitative (18)F-FDG uptake, (P = 0.0029), elevated plasma concentrations of biomarkers of platelets (P-selectin, P = 0.0009) and thrombin activation (TAT complexes, P = 0.0075), and fibrinolysis (PAP complexes, P < 0.0001; D-dimers, P = 0.0006). Plasma markers of coagulation and fibrinolysis were related to false channel morphology, suggesting that thrombus biological dynamics may drive progressive expansion of type B dissections. Enhanced FDG uptake may be considered as a complementary imaging marker associated with secondary complications in type B dissections. During follow-up, aneurysmal progression is related to PET/CT and biomarkers of thrombus renewal and lysis.

Uptake of aortic 18F-FDG is correlated with low-density lipoprotein cholesterol and leptin in a general population.

ObjectiveThis study investigated the relationship between aortic 18F-fluoro-2-deoxy-D-glucose (18F-FDG) uptake and clinical and laboratory findings related to atherosclerosis in a general population.Methods 18F-FDG uptake in the ascending aorta was measured on the positron emission tomography/computed tomography (PET/CT) scans of 211 Japanese adults. The maximum target-to-background ratio (TBR) was compared with clinical and laboratory atherosclerosis findings.ResultsBy multivariate regression analysis adjusted for age and sex, TBR-ascending aorta (TBR-A) was significantly correlated with various clinical and laboratory parameters, such as body mass index, log visceral fat area, low-density lipoprotein cholesterol (LDL-C), log fasting immunoreactive insulin, log homeostasis model assessment of insulin resistance, log total adiponectin and log-leptin, in all subjects. Furthermore, by multivariate linear regression analysis adjusted for confounding factors, TBR-A was significantly correlated with LDL-C (β = 0.001, p = 0.03) and log-leptin (β = 0.336, p<0.01) in all subjects.ConclusionTBR-A was significantly correlated with LDL-C and log-leptin independent from confounding factors. Our results suggest that aortic 18F-FDG uptake is a good marker of atherosclerosis, even in a general population.

Lipid lowering and imaging protease activation in atherosclerosis

BackgroundLipid lowering is a mainstay of modern therapeutic approach to atherosclerosis. We sought to evaluate matrix metalloproteinase (MMP)-targeted microSPECT imaging for tracking of the effect of lipid-lowering interventions on plaque biology in atherosclerotic mice in vivo. Methods and ResultsApoE−/− mice fed on a high fat diet (HFD) for 2 months were randomly assigned to continuation of HFD, HFD plus simvastatin, HFD plus fenofibrate and high fat withdrawal (HFW). The animals underwent serial microSPECT/CT imaging using RP805, a 99mTc-labeled MMP-targeted tracer at 1 and 4 weeks after randomization. All three interventions reduced total blood cholesterol by 4 weeks. In animals on HFD, aortic arch RP805 uptake significantly increased from 1 week to 4 weeks. Tracer uptake in fenofibrate and HFW groups was significantly lower than uptake in the HFD group at 4 weeks. Similarly, CD 68 gene expression, reflecting plaque inflammation, was significantly lower in fenofibrate and HFW groups compared to HFD group. MMP tracer uptake significantly correlated with aortic CD68, but not VE-cadherin or smooth muscle α-actin expression. ConclusionsMMP tracer uptake paralleled the effect of lipid-lowering interventions on plaque inflammation in atherosclerotic mice. MMP-targeted imaging may be used to track the effect of therapeutic interventions in atherosclerosis.

18F-Sodium Fluoride Uptake Is a Marker of Active Calcification and Disease Progression in Patients With Aortic Stenosis

18F-Sodium fluoride (18F-NaF) and 18F-fluorodeoxyglucose (18F-FDG) are promising novel biomarkers of disease activity in aortic stenosis. We compared 18F-NaF and 18F-FDG uptake with histological characterization of the aortic valve and assessed whether they predicted disease progression. Thirty patients with aortic stenosis underwent combined positron emission and computed tomography using 18F-NaF and 18F-FDG radiotracers. In 12 patients undergoing aortic valve replacement surgery (10 for each tracer), radiotracer uptake (mean tissue/ =0.65; P=0.04) and osteocalcin (r=0.68; P=0.03) immunohistochemistry. There was no significant correlation between 18F-FDG uptake and CD68 staining (r=-0.43; P=0.22). After 1 year, aortic valve calcification increased from 314 (193-540) to 365 (207-934) AU (P<0.01). Baseline 18F-NaF uptake correlated closely with the change in calcium score (r=0.66; P<0.01), and this improved further (r=0.75; P<0.01) when 18F-NaF uptake overlying computed tomography-defined macrocalcification was excluded. No significant correlation was noted between valvular 18F-FDG uptake and change in calcium score (r=-0.11; P=0.66). 18F-NaF uptake identifies active tissue calcification and predicts disease progression in patients with calcific aortic stenosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01358513.

Biologically Inspired Stealth Peptide-Capped Gold Nanoparticles

Introduction into the human body makes most nanoparticle systems susceptible to aggregation via nonspecific protein binding. Here, we developed a peptide-capped gold nanoparticle platform that withstands aggregation in undiluted human serum at 37 °C for 24 h. This biocompatible and natural system is based on mimicking human proteins which are enriched in negatively charged glutamic acid and positively charged lysine residues on their surface. The multifunctional EKEKEKE-PPPPC-Am peptide sequence consists of a stealth glutamic acid/lysine portion combined with a surface anchoring linker containing four prolines and a cysteine. Particle stability was measured via optical spectroscopy and dynamic light scattering in single protein, high salt, and undiluted human serum solutions. In vitro cell experiments demonstrate EKEKEKE-PPPPC-Am capped gold nanoparticles effectively minimize nonspecific cell uptake by nonphagocytic bovine aortic endothelial cells and phagocytic murine macrophage RAW 264.7 cells. Cytotoxicity studies show that peptide-capped gold nanoparticles do not affect cell viability. Finally, the peptide EKEKEKE-PPPPC-Am was extended with cyclic RGD to demonstrate specific cell targeting and stealth without using poly(ethylene glycol). Adding the functional peptide via peptide sequence extension avoids complex conjugation chemistries that are used for connection to synthetic materials. Inductively coupled plasma mass spectroscopy results indicate high aortic bovine endothelial cell uptake of c[RGDfE(SGG-KEKEKE-PPPPC-Am)] capped gold nanoparticles and low uptake of the control scrambled sequence c[RDGfE(SGG-KEKEKE-PPPPC-Am)] capped gold nanoparticles.

Impaired L-Arginine Uptake But Not Arginase Contributes to Endothelial Dysfunction in Rats With Chronic Kidney Disease

Reduced nitric oxide bioavailability contributes to increased cardiovascular disease risk in patients with chronic kidney disease (CKD). Arginase has been implicated as a potential therapeutic target to treat vascular dysfunction by improving substrate availability for endothelial nitric oxide synthase. The purpose of this study was to determine if arginase contributes to endothelial dysfunction in the 5/6 ablation infarction (AI) rat model of CKD. Endothelium-dependent relaxation of aortic rings to acetylcholine was significantly impaired in AI animals versus sham after 8 weeks and was not improved by arginase inhibition (S-(2-Boronoethyl)-L-cysteine hydrochloride) alone or in combination with L-arginine. Additionally, scavenging of superoxide (Tempol, Tempol + L-arginine, Tempol + L-arginine + S-(2-Boronoethyl)-L-cysteine hydrochloride) was not effective, suggesting that a mechanism independent of oxidative stress contributes to endothelium-dependent relaxation in moderate to severe CKD. Aortic uptake of radiolabeled L-arginine was attenuated in AI animals and was associated with a reduced expression of the L-arginine transporter CAT-1. These data suggest that arginase does not contribute to endothelial dysfunction in CKD; however, impaired L-arginine transport may play an important role in diminishing substrate availability for nitric oxide production leading to endothelial dysfunction.

Aortic 18F-FDG PET/CT uptake pattern at 60 min (early) and 180 min (delayed) acquisition in a control population

18F-Fluoro-2-deoxy-D-glucose (F-FDG) PET/CT acquisition is generally performed 60 min after injection. The normal biodistribution pattern of F-FDG includes activity in the aortic territory due to blood pool activity, which could interfere in the diagnosis of aortic diseases by overlapping the wall uptake. The aim of the study was to evaluate the change over time of F-FDG uptake by the aortic wall and the activity in the lumen in a control population and to establish normal reference values. This prospective study included 15 control patients (mean age: 58.2 years). PET/CT was acquired 60 min (early scan) and 180 min (delayed scan) after an F-FDG injection at a dose of 7 MBq/kg. A visual and semiquantitative analysis of the F-FDG aortic wall uptake was carried out, and lumen activity and the aortic wall to lumen ratio [target-to-background ratio (TBR)] were determined. In the visual analysis all patients showed F-FDG activity at the aortic territory at 60 and 180 min. The pattern of uptake at 60 min was diffuse in all 15 patients (100%), without delineation of the aortic wall uptake; however, at 180 min the uptake pattern of the aortic wall changed to lineal in 14 patients (93.3%). The aortic wall maximum standardized uptake value decreased from 2.07±0.34 to 1.7±0.46 during the delayed acquisition (P=0.0279) and the lumen maximum standardized uptake value decreased highly significantly (1.99±0.35 vs. 1.36±0.32, P=0.0001). Therefore, TBR also increased highly significantly from 1.04±0.06 to 1.25±0.16 (P<0.0001). The high decrease in blood pool activity from 60 to 180 min provides a better delineation of the aortic wall uptake, which corresponds to the normal pattern at that time. The TBR increased significantly at 180 min, and 1.25±0.16 is suggested as the threshold for diagnostic purposes, especially for the diagnosis of vasculitis.

Delayed time-point 18F-FDG PET CT imaging enhances assessment of atherosclerotic plaque inflammation

The aim of this study was to determine the ideal circulation time of fluorine-18 fluorodeoxyglucose (F-FDG) in order to detect and quantify atherosclerotic plaque inflammation with PET computed tomography (CT) imaging. Fifteen patients underwent multiple time-point imaging at ∼60, 120, and 180 min after F-FDG administration. For each time point, global assessment of aortic and carotid F-FDG uptake was determined qualitatively by visual assessment and semiquantitatively by calculation of the mean and maximum standardized uptake values (SUV) and the corresponding target-to-background ratio (TBR). Delayed imaging achieved significant improvement in visualization of atherosclerotic plaque inflammation [Friedman's χ statistic (d.f.=2, n=15)=24.13, P<0.001, Kendall's W=0.80]. This observation was confirmed by semiquantitative image analysis. At 1 h, the aortic and carotid SUVmean-calculated TBR was 1.05 [95% confidence interval (CI)=0.98, 1.11] and 0.88 (95% CI=0.81, 0.96), respectively. At 3 h, the TBR significantly increased to 1.57 (95% CI=1.28, 1.86; P=0.001) for the aorta and to 1.61 (95% CI=1.36, 1.87; P<0.001) for the carotid arteries. SUVmax-calculated TBRs showed a similar increase over time. One- and 2-h F-FDG PET CT imaging is suboptimal for global assessment of atherosclerotic plaque inflammation compared with imaging at 3 h. Our data support the utilization of 3-h delayed imaging to obtain optimal data for the detection and quantification of atherosclerotic plaque inflammation in human arteries.

Integrin-Targeted Molecular Imaging of Experimental Abdominal Aortic Aneurysms by 18 F-labeled Arg-Gly-Asp Positron-Emission Tomography

Both inflammation and neoangiogenesis contribute to abdominal aortic aneurysm (AAA) disease. Arg-Gly-Asp-based molecular imaging has been shown to detect the integrin αvβ3. We studied a clinical dimeric (18)F-labeled Arg-Gly-Asp positron-emission tomography (PET) agent ((18)F-FPPRGD2) for molecular imaging of experimental AAAs. Murine AAAs were induced in Apo-E-deficient mice by angiotensin II infusion, with monitoring of aortic diameter on ultrasound. AAA (n=10) and saline-infused control mice (n=7) were injected intravenously with (18)F-FPPRGD2, as well as an intravascular computed tomography contrast agent, then scanned using a small-animal PET/computed tomography scanner. Aortic uptake of (18)F-FPPRGD2 was quantified by percentage-injected dose per gram and target-to- =0.003; median target-to- =0.0008). Ex vivo autoradiography demonstrated high uptake of (18)F-FPPRGD2 into the AAA wall, with immunohistochemistry showing substantial cluster of differentiation (CD)-11b(+) macrophages and CD-31(+) neovessels. Target-to- =-0.29, P=0.41) but did strongly correlate with both mural macrophage density (r=0.79, P=0.007) and neovessel counts (r=0.87, P=0.001) on immunohistochemistry. PET imaging of experimental AAAs using (18)F-FPPRGD2 detects biologically active disease, correlating to the degree of vascular inflammation and neoangiogenesis. This may provide a clinically translatable molecular imaging approach to characterize AAA biology to predict risk beyond size alone.

Response to Letter Regarding Article, “Anti–Tumor Necrosis Factor-α Therapy Reduces Aortic Inflammation and Stiffness in Patients With Rheumatoid Arthritis”

We thank the authors for their interest in our study.1 They raise several relevant points, which we address below. We agree that further work is needed to ascertain the origin of 18F-fluoro-deoxyglucose (FDG) uptake in patients with rheumatoid arthritis. Although we cannot be certain, we feel that subclinical vasculitis is the most likely explanation for our findings for several reasons. First, we compared aortic FDG uptake in rheumatoid arthritis subjects with an atherosclerotic population with stable cardiovascular disease, matched for age. We were careful to exclude those rheumatoid arthritis subjects with established cardiovascular disease or diabetes mellitus. Even so, we found that the aortic FDG uptake …

FRI0476 Relative fdg accumulation of the aortic wall lesions to aortic blood pool in 18f-fdg-pet and pet/ct is a useful parameter for assessing the disease activity of takayasu arteritis

BackgroundThere is accumulating evidence that 18F-fluolodeoxyglucose-positron emission tomography (FDG-PET) and PET/ computed tomography (PET/CT) is useful for monitoring patients with Takayasu arteritis (TA).ObjectivesTo investigate a quantitative indicator in FDG-PET or...