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Purpose: To assess in healthy volunteers the whole-body distribution and dosimetry of [11C]metoclopramide, a new positron emission tomography (PET) tracer to measure P-glycoprotein activity at the blood-brain barrier. Procedures: Ten healthy volunteers (five women, five men) were intravenously injected with 387 ± 49 MBq of [11C]metoclopramide after low dose CT scans and were then imaged by whole-body PET scans from head to upper thigh over approximately 70 min. Ten source organs (brain, thyroid gland, right lung, myocardium, liver, gall bladder, left kidney, red bone marrow, muscle and the contents of the urinary bladder) were manually delineated on whole-body images. Absorbed doses were calculated with QDOSE (ABX-CRO) using the integrated IDAC-Dose 2.1 module. Results: The majority of the administered dose of [11C]metoclopramide was taken up into the liver followed by urinary excretion and, to a smaller extent, biliary excretion of radioactivity. The mean effective dose of [11C]metoclopramide was 1.69 ± 0.26 μSv/MBq for female subjects and 1.55 ± 0.07 μSv/MBq for male subjects. The two organs receiving the highest radiation doses were the urinary bladder (10.81 ± 0.23 μGy/MBq and 8.78 ± 0.89 μGy/MBq) and the liver (6.80 ± 0.78 μGy/MBq and 4.91 ± 0.74 μGy/MBq) for female and male subjects, respectively. Conclusions: [11C]Metoclopramide showed predominantly renal excretion, and is safe and well tolerated in healthy adults. The effective dose of [11C]metoclopramide was comparable to other 11C-labeled PET tracers. [ABSTRACT FROM AUTHOR]

Objective: The pancreatic uptake of [11C]methionine ([11C]MET) is associated with beta-cell function and insulin secretion, but [11C]MET uptake and its relationship with exocrine pancreatic performance are less well studied. The postprandial release of cholecystokinin (CCK) depends on gastric emptying velocity and triggers exocrine pancreas secretion. Therefore, we assumed that high postprandial CCK concentrations stimulate the uptake of [11C]MET in the residual pancreas following pancreaticoduodenectomy. Methods: Nineteen tumor-free patients after pancreaticoduodenectomy (median age: 64; 25/75 quantile: 56–67 years); ten males, nine females and ten healthy controls (median age: 24; 25/75 quantile: 23.8–26 years) were given a mixed meal. Plasma CCK, insulin and glucose concentrations were measured before and at 10, 20, 30, 60, 90, 150 and 180 min after ingestion. Simultaneously, 800 MBq of [11C]MET were administered and the activity [maximum tissue standardized uptake values (SUVmax)] over the pancreas was measured using PET-CT at 15, 30 and 60 min after injection. Results: Integrated CCK (AUC30) correlated with SUVmax (AUC60, R2 = 0.45, p value = 0.0013). Multivariate analysis revealed postprandial insulin (AUC60) and CCK concentrations and young age as significant independent predictors of [11C] methionine uptake. Conclusion: The association between CCK concentrations and pancreatic [11C]MET uptake might indicate a causal relationship. Further research should assess whether [11C]MET uptake could serve as a less invasive tool to assess exocrine pancreas activity. [ABSTRACT FROM AUTHOR]

Purpose: PET/MRI has recently been introduced into clinical practice. We prospectively investigated the clinical impact of PET/MRI compared with PET/CT, in a mixed population of cancer patients, and performed an economic evaluation of PET/MRI. Methods: Cancer patients referred for routine staging or follow-up by PET/CT underwent consecutive PET/CT and PET/MRI, using single applications of [18F]FDG, [68Ga]Ga-DOTANOC, or [18F]FDOPA, depending on tumor histology. PET/MRI and PET/CT were rated separately, and lesions were assessed per anatomic region; based on regions, per-examination and per-patient accuracies were determined. A simulated, multidisciplinary team meeting served as reference standard and determined whether differences between PET/CT and PET/MRI affected patient management. The McNemar tests were used to compare accuracies, and incremental cost-effectiveness ratios (ICERs) for PET/MRI were calculated. Results: Two hundred sixty-three patients (330 same-day PET/CT and PET/MRI examinations) were included. PET/MRI was accurate in 319/330 examinations and PET/CT in 277/330 examinations; the respective accuracies of 97.3% and 83.9% differed significantly (P < 0.001). The additional findings on PET/MRI—mainly liver and brain metastases—had implications for patient management in 21/263 patients (8.0%). The per-examination cost was 596.97 EUR for PET/MRI and 405.95 EUR for PET/CT. ICERs for PET/MRI were 14.26 EUR per percent of diagnostic accuracy and 23.88 EUR per percent of correctly managed patients. Conclusions: PET/MRI enables more appropriate management than PET/CT in a nonnegligible fraction of cancer patients. Since the per-examination cost is about 50% higher for PET/MRI than for PET/CT, a histology-based triage of patients to either PET/MRI or PET/CT may be meaningful. [ABSTRACT FROM AUTHOR]

Background: At the time of diagnosis, one-third of medullary thyroid carcinoma (MTC) patients show lymph node (LN) or distant metastasis. A metastasized MTC requires different surgical strategies.Objective: This study aimed to determine the value of ultrasound and [18F]fluoro-dihydroxyphenylalanine positron emission tomography with computed tomography (F-DOPA-PET-CT) in localizing MTC, as well as LN and distant metastasis.Methods: The study included 50 patients (24 males/26 females) with preoperative ultrasound, F-DOPA-PET-CT, and histologically proven MTC. Imaging results were correlated with both preoperative basal calcitonin (bCt) levels and final histology.Results: Tumors were classified as pT1a:17 (diameter, mean ± standard deviation: 5.8 ± 3.0 mm), pT1b:15 (15.0 ± 3.2 mm), pT2:9 (27.3 ± 7.0 mm), and pT3:9 (38.3 ± 24.2 mm). The median bCt level was 202 pg/mL (lower/upper quartile: 82/1074 pg/mL). Ultrasound was positive for tumor in 45/50 (92%) patients (20.0 ± 16.0 mm) and negative in 5 patients (3.2 ± 2.2 mm). Overall, 43/50 (86%) patients had positive F-DOPA local scans (20.0 ± 16.4 mm), while 7 (14%) patients were negative (7.7 ± 8.1 mm). Lastly, 21/50 (42%) patients had LN metastasis; 8/21 (38%) patients had positive LNs suspected with ultrasound, and 12/21 (57%) patients had positive LNs suspected with F-DOPA. Tumor and LN sensitivity of ultrasound was 92% and 43%, respectively, and 86% and 57% of F-DOPA-PET-CT, respectively. In 3/50 (6%) patients and 3/50 (6%) patients, mediastinal LN metastasis and distant metastasis, respectively, were diagnosed only by F-DOPA-PET-CT.Conclusion: Ultrasound and F-DOPA-PET-CT are sensitive for the localization of MTC but not for the presence and location of LN metastasis (limitations: size/number). Only F-DOPA ensures the diagnosis of distant metastasis and influences the extent of LN surgery. Surgical strategy cannot be predicted based on neither ultrasound nor F-DOPA-PET-CT. [ABSTRACT FROM AUTHOR]

Purpose: To investigate [11C]acetate PET-surrogate parameter of fatty acid synthase activity—as suitable tool for diagnosis and monitoring of liver steatosis.Methods: In this retrospective study, data were obtained from 83 prostatic carcinoma patients from 1/2008 to 1/2014. Mean HU was calculated from unenhanced CT of all patients from liver with liver HU less than 40 as threshold for liver steatosis. SUVmax of the liver and of the blood pool in thoracic aorta (as background for calculation of a liver/background ratio [SUVl/b]) was measured. t test was used with a P < 0.05 considered as statistically significant difference and ROC analysis was used for calculating specificity and sensitivity.Results: 19/83 patients (20%) had diagnosis of hepatic steatosis according to CT. Uptake of [11C]acetate was significantly higher in patients with hepatic steatosis as compared to control group (SUVmax 7.96 ± 2.0 vs. 5.48 ± 2.3 [P < 0.001]). There was also a significant correlation between both SUVmax (r = − 0.52, P < 0.001) and SUVl/b (r = − 0.59, P < 0.001) with the density (HU) of the liver. In ROC analysis for detection of liver steatosis SUVmax (threshold: 5.86) had a sensitivity of 94% and specificity of 69% with an AUC of 0.81. Increasing body mass index is correlated with the severity of steatosis.Conclusion: We showed for the first time that hepatic steatosis associates with increased [11C]acetate uptake. Also, severity of steatosis correlates with [11C]acetate uptake. [11C]acetate uptake PET seems promising for the assessment of liver steatosis. [ABSTRACT FROM AUTHOR]

Purpose: Medullary thyroid carcinoma (MTC) is characterized by a high rate of metastasis. In this study we evaluated the ability of [18F]DOPA PET/ceCT to stage MTC in patients with suspicious thyroid nodules and pathologically elevated serum calcitonin (Ctn) levels prior to total thyroidectomy and lymph node (LN) dissection.Methods: A group of 32 patients with sonographically suspicious thyroid nodules and pathologically elevated basal Ctn (bCtn) and stimulated Ctn (sCtn) levels underwent DOPA PET/ceCT prior to surgery. Postoperative histology served as the standard of reference for ultrasonography and DOPA PET/ceCT region-based LN staging. Univariate and multivariate regression analyses as well as receiver operating characteristic analysis were used to evaluate the correlations between preoperative and histological parameters and postoperative tumour persistence or relapse.Results: Primary MTC was histologically verified in all patients. Of the 32 patients, 28 showed increased DOPA decarboxylase activity in the primary tumour (sensitivity 88%, mean SUVmax 10.5). Undetected tumours were exclusively staged pT1a. The sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53% and 73%, in contrast to 20% and 39%, respectively, for neck ultrasonography. Preoperative bCtn and carcinoembryonic antigen levels as well as cN1b status and the number of involved neck regions on DOPA PET/ceCT were predictive of postoperative tumour persistence/relapse in the univariate regression analysis (P < 0.05). Only DOPA PET/ceCT cN1b status remained significant in the multivariate analysis (P = 0.016, relative risk 4.02).Conclusion: This study revealed that DOPA PET/ceCT has high sensitivity in the detection of primary MTC and superior sensitivity in the detection of LN metastases compared to ultrasonography. DOPA PET/ceCT identification of N1b status predicts postoperative tumour persistence. Thus, implementation of a DOPA-guided LN dissection might improve surgical success. [ABSTRACT FROM AUTHOR]

Purpose: Imaging biomarkers assessed with magnetic resonance imaging (MRI) and/or positron emission tomography (PET) enable non-invasive tumor characterization in cervix cancer patients. We investigated the spatio-temporal stability of hypoxia, perfusion, and the cell density of tumors over time by repetitive imaging prior to, during, and after radio-chemotherapy.Procedures: Thirteen patients were included in this prospective study. The imaging protocol included the following: [18F]fluoromisonidazole ([18F]FMISO)-PET/x-ray computed tomography (CT) and multiparametric (mp)-MRI at four time-points (TP): baseline (BL); and weeks 2 (TP1), 5 (TP2), and 19 after treatment start (follow-up FU). Complete datasets for six patients could be assessed for tumor volume, enhancement kinetics, diffusivity, and [18F]FMISO-avidity (P1-P6). In addition, two patients completed all PET/CT examinations (P7-P8) but not all MR scans; however, one of them had no hypoxia (P8). Descriptive statistics, correlations, and voxel-by-voxel analysis were performed. For various, independent reasons, five patients could not complete the study according to the protocol with all imaging sequences.Results: Median tumor ADCs (in ×10-3 mm2/s) were 0.99 ± 0.10 at BL, 1.20 ± 0.12 at TP1, 1.33 ± 0.14 at TP2, and 1.38 ± 0.21 at FU. The median TBRpeak (tumor-to-background) was 2.7 ± 0.8 at BL, 1.6 ± 0.2 at TP1, 1.8 ± 0.3 at TP2, and 1.7 ± 0.3 at FU. The voxel-by-voxel analysis of the [18F]FMISO uptake at BL and TP1 showed no correlation. Between TP2 and TP1 and FU and TP2, weak correlations were found for two patients.Conclusions: Longitudinal mp-MR and PET imaging enables the in vivo tumor characterization over time. While perfusion and cell density decreased, there was a non-uniform change of hypoxia observed during radiotherapy. To assess the potential impact with regard to more personalized treatment approaches, hypoxia imaging-based dose painting for cervix cancer requires further research. [ABSTRACT FROM AUTHOR]

In melanoma, therapies with inhibitors to oncogenic BRAFV600E are highly effective but responses are often short-lived due to the emergence of drug-resistant tumor subpopulations. We describe here a mechanism of acquired drug resistance through the tumor microenvironment, which is mediated by human tumor-associated B cells. Human melanoma cells constitutively produce the growth factor FGF-2, which activates tumor-infiltrating B cells to produce the growth factor IGF-1. B-cell-derived IGF-1 is critical for resistance of melanomas to BRAF and MEK inhibitors due to emergence of heterogeneous subpopulations and activation of FGFR-3. Consistently, resistance of melanomas to BRAF and/or MEK inhibitors is associated with increased CD20 and IGF-1 transcript levels in tumors and IGF-1 expression in tumor-associated B cells. Furthermore, first clinical data from a pilot trial in therapy-resistant metastatic melanoma patients show anti-tumor activity through B-cell depletion by anti- CD20 antibody. Our findings establish a mechanism of acquired therapy resistance through tumor-associated B cells with important clinical implications. [ABSTRACT FROM AUTHOR]

Purpose: [ S-methyl-C]-L-methionine ([C]MET) uptake in the pancreas might be a central indicator of beta cell function. Since gastric emptying was recently shown to influence glycemic control in subjects after pancreaticoduodenectomy (PD, the surgical treatment of neoplasms of the pancreas head), we looked for imaginable relationships between gastric emptying, pre- and postprandial insulin concentrations, and [C]MET uptake. Methods: Nineteen tumor-free survivors after PD (age mean ± SD: 61 ± 8.7 yrs.; 10 male, 9 female) and 10 healthy controls (age: 27 ± 8.7 yrs.; 7 male, 3 female) were given a mixed test meal. One gram of paracetamol was ingested with the meal to evaluate the speed of gastric emptying. Insulin, glucose, and paracetamol plasma concentrations were measured before and over 180 minutes after ingestion. Beta cell function was calculated from fasting glucose and insulin plasma concentrations. Simultaneously, 800 MBq of [C]MET were administered and the activity (maximum tissue standardized uptake values [SUVmax]) over the pancreas was measured at 15, 30, and 60 minutes after injection. Total integrated SUVmax (area under the curve [AUC]) and incremental SUVmax were calculated. Results: The uptake of [C]MET in the pancreas was significantly higher ( p < 0.0001) in controls compared to the PD group. Gastric emptying was significantly slower in controls compared to pancreatectomy subjects ( p < 0.0001). Paracetamol AUC correlated with the SUVmax increment between 15 and 30 minutes (R = 0.27, p = 0.0263), suggesting a relationship between gastric emptying and the uptake of [C]MET. Total integrated SUVmax correlated with insulin AUC (R = 0.66, p < 0.0001) in patients after PD. Multivariate regression analysis revealed insulin AUC and beta cell function, calculated from the fasting insulin to glucose ratio, as independent predictors of C-methionine uptake, i.e. total integrated SUVmax, in patients after PD (R = 0.78, p < 0.0001). Conclusion: Postprandial [C]MET uptake may represent basal and postprandial beta cell function. The findings suggest a possible usefulness of this imaging procedure for further studying beta cell function. [ABSTRACT FROM AUTHOR]

Fever of unknown origin (FUO) was originally characterised in 1961 by Petersdorf and Beeson as a disease condition of temperature exceeding 38.3 °C on at least three occasions over a period of at least three weeks, with no diagnosis made despite one week of inpatient investigation. However, since underlying diseases are often reported for classical FUO, these presentations may not be considered to be of 'unknown origin'. Rather, the aetiology of prolonged fever may resolve, or not resolve. The definition of fever with unresolved cause (true FUO) is difficult, as it is a moving target, given the constant advancement of imaging and biomarker analysis. Therefore, the prevalence of fever with unresolved cause (FUO) is unknown. In this review, we report such a case of prolonged fever, which initially has presented as classical FUO, and discuss current literature. Furthermore, we will give an outlook, how a prospective study on FUO will allow to solve outstanding issues like the utility of different diagnostic investigations, and the types and prevalence of various underlying diseases. [ABSTRACT FROM AUTHOR]

Purpose: To compare the diagnostic accuracy of prone F-FDG PET/CT with that of contrast-enhanced MRI (CE-MRI) at 3 T in suspicious breast lesions. To evaluate the influence of tumour size on diagnostic accuracy and the use of maximum standardized uptake value (SUV) thresholds to differentiate malignant from benign breast lesions. Methods: A total of 172 consecutive patients with an imaging abnormality were included in this IRB-approved prospective study. All patients underwent F-FDG PET/CT and CE-MRI of the breast at 3 T in the prone position. Two reader teams independently evaluated the likelihood of malignancy as determined by F-FDG PET/CT and CE-MRI independently. F-FDG PET/CT data were qualitatively evaluated by visual interpretation. Quantitative assessment was performed by calculation of SUV. Sensitivity, specificity, diagnostic accuracy, area under the curve and interreader agreement were calculated for all lesions and for lesions <10 mm. Histopathology was used as the standard of reference. Results: There were 132 malignant and 40 benign lesions; 23 lesions (13.4 %) were <10 mm. Both F-FDG PET/CT and CE-MRI achieved an overall diagnostic accuracy of 93 %. There were no significant differences in sensitivity ( p = 0.125), specificity ( p = 0.344) or diagnostic accuracy ( p = 1). For lesions <10 mm, diagnostic accuracy deteriorated to 91 % with both F-FDG PET/CT and CE-MRI. Although no significant difference was found for lesions <10 mm, CE-MRI at 3 T seemed to be more sensitive but less specific than F-FDG PET/CT. Interreader agreement was excellent ( κ = 0.85 and κ = 0.92). SUV threshold was not helpful in differentiating benign from malignant lesions. Conclusion: F-FDG PET/CT and CE-MRI at 3 T showed equal diagnostic accuracies in breast cancer diagnosis. For lesions <10 mm, diagnostic accuracy deteriorated, but was equal for F-FDG PET/CT and CE-MRI at 3 T. For lesions <10 mm, CE-MRI at 3 T seemed to be more sensitive but less specific than F-FDG PET/CT. Quantitative assessment using an SUV threshold for differentiating benign from malignant lesions was not helpful in breast cancer diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: To compare fused gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI (diffusion-weighted imaging) for the assessment of abdominal neuroendocrine tumours (NETs). Methods: Eighteen patients with suspected or histologically proven NETs of the abdomen were enrolled in this retrospective study. All patients underwent Ga-68-DOTANOC PET/CT for a primary search, staging, or restaging, and received an additional MRI, including dynamic gadoxetate-enhanced T1-weighted sequences and DWI (b-values 50, 300 and 600). Co-registered gadoxetate-enhanced PET/MRI and PET/DWI were separately analysed for NET lesions by a nuclear medicine physician and a radiologist in consensus. Sensitivity and specificity were calculated on a per-region, per-organ and per-patient basis. Results: Eighty-seven out of 684 anatomical regions, and 23 out of 270 organs, were NET-positive in 14 out of 18 patients. Region-based sensitivities and specificities were 97.7 % and 99.7 % for gadoxetate-enhanced PET/MRI and 98.9 % and 99.7 % for PET/DWI. Organ-based sensitivities and specificities were 91.3 % and 99.6 % for gadoxetate-enhanced PET/MRI and 95.7 % and 99.6 % for PET/DWI. Finally, patient-based sensitivities and specificities were 100 % and 100 % for gadoxetate-enhanced PET/MRI and 100 % and 75 % for PET/DWI. Sensitivities and specificities of the two methods did not differ significantly. Conclusions: Gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI are equally useful for the assessment of abdominal NETs. Key Points: • Positron emission tomography and magnetic resonance imaging can both assess neuroendocrine tumours. • Fusion of PET/MR imaging provides helpful information. • Gadoxetate-enhanced Ga-68-DOTANOC PET/MRI and Ga-68-DOTANOC PET/DWI assess neuroendocrine tumours equally well. • PET/DWI is inherently simpler than gadoxetate-enhanced PET/MRI. • Only benign hepatic lesions pose a potential diagnostic dilemma for PET/DWI. [ABSTRACT FROM AUTHOR]

Objectives: To determine, in patients with melanoma, the dependence of PET sensitivity on pulmonary metastasis size, and to determine patients who require further evaluation for definite staging.Methods: Of 183 melanoma patients who underwent (18)F-fluorodeoxyglucose PET/computed tomography (CT) for staging or follow-up between January 2008 and June 2011, 38 patients (18 women and 20 men; mean age 62.0 ± 14.7 years) with one or more pulmonary metastases visible on CT were included in the retrospective study. Each pulmonary metastasis was rated as positive or negative on PET, and lesion size (maximum transverse diameter) was assessed on CT. PET sensitivity was calculated according to the lesions' size, in 2-mm steps.Results: A total of 181 pulmonary metastases were analysed. PET sensitivity was 7.9 % for lesions of 4-5 mm; 33.3 % for lesions of 6-7 mm; 56.8 % for lesions of 8-9 mm; 63.6 % for lesions of 10-11 mm; 100 % for lesions of 12-14 mm; and 100 % for lesions of at least 15 mm. The differences in sensitivity between the size groups were significant (P < 0.001) CONCLUSIONS: With current state-of-the-art PET/CT technology, additional tests are necessary for definitive staging of melanoma patients who have one or more PET-negative lung nodules less than 12 mm in diameter on expiratory CT.Key Points: • PET cannot rule out malignancy in pulmonary nodules less than 12 mm on expiratory CT. • Melanoma patients with PET-negative pulmonary nodules less than 12 mm require additional tests. • Knowledge of these factors can help interpretation of PET and PET/CT findings. [ABSTRACT FROM AUTHOR]

Objectives: To determine the value of intravenous contrast medium in (68)Ga-DOTA-Phe(1)-Tyr(3)-octreotide - (68)Ga-DOTATOC - PET/CT for the detection of abdominal neuroendocrine tumours (NET). Methods: In fifty-five patients with known or suspected NETs of the abdomen PET/CT was performed on a 64-row multi-detector hybrid system. For PET, 150 MBq of (68)Ga-DOTATOC were injected intravenously. Full-dose unenhanced, and arterial- and venous-phase contrast-enhanced CT images were obtained. Unenhanced and contrast-enhanced PET/CT images were evaluated separately for the presence of NETs on a per-region basis, by two separate teams with different experience levels. Results: On unenhanced PET/CT, sensitivity and specificity ranged from 89.3% (junior team) to 92% (senior team), and 99.1% (junior team) to 99.2% (senior team), respectively. On contrast-enhanced PET/CT, sensitivity and specificity ranged from 92.3% (junior team) to 98.5% (senior team), and 99.4% (junior team) to 99.5% (senior team), respectively. These increases in sensitivity and specificity, due to the use of contrast-enhanced images, were statistically significant ( P < 0.05). Conclusions: Intravenous contrast medium only moderately, aleit significantly, improves the sensitivity of (68)Ga-DOTATOC PET/CT for the detection of abdominal NETs, and hardly affects specificity. Thus, while contrast enhancement is justified to achieve maximum sensitivity, unenhanced images may be sufficient for routine PET/CT in NET patients. Key Points: • Contrast media moderately improve the sensitivity of (68)Ga-DOTATOC PET/CT for neuroendocrine tumours. • Contrast media hardly affect the specificity of (68)Ga-DOTATOC PET/CT for neuroendocrine tumours. • Unenhanced PET/CT is sufficient for routine imaging of patients with neuroendocrine tumours. [ABSTRACT FROM AUTHOR]

Purpose: Cardiac contractility modulation (CCM) is a device-based therapy that involves delivery of nonexcitatory electrical signals resulting in improved ventricular function and a reversal of maladaptive cardiac fetal gene programmes. Our aim was to evaluate whether acute application of CCM leads to an increase in myocardial oxygen consumption (MVO) in patients with chronic heart failure using C-acetate positron emission tomography (PET). Methods: We prospectively enrolled 21 patients with severe heart failure. C-acetate PET was performed before and after activation of the CCM device. In 12 patients an additional stress study with dobutamine was performed. Results: Under resting conditions, the values of myocardial blood flow (MBF), MVO and work metabolic index (WMI, reflecting myocardial efficiency) with the CCM device activated did not differ significantly from the values with the device deactivated. MBF was 0.81 ± 0.18 ml min g with the device off and 0.80 ± 0.15 ml min g with the device on ( p = 0.818), MVO was 6.81 ± 1.69 ml/min/100 g with the device off and 7.15 ± 1.62 ml/min/100 g with the device on ( p = 0.241) and WMI was 4.94 ± 1.14 mmHg ml/m with the device off and 5.21 ± 1.36 mmHg ml/m with the device on ( p = 0.344). Under dobutamine stress, the values of MBF, MVO and WMI with the CCM device activated did not differ from the values with the device deactivated, but were significantly increased compared with the values obtained under resting conditions. Conclusion: These results indicate that CCM does not induce increased MVO, even under stress conditions. [ABSTRACT FROM AUTHOR]

Purpose: 11β-Hydroxylase is a key enzyme in the biosynthesis of adrenocortical steroid hormones and is a suitable target for the imaging of the adrenal cortex. [11C]Metomidate (MTO), [11C]etomidate (ETO) and desethyl-[18F]fluoroethyl-etomidate (FETO) are potent inhibitors of this enzyme and are used for PET imaging of adrenocortical pathologies. The aims of this study were (1) to evaluate and compare the metabolic stability of MTO, ETO and FETO against esterases and (2) to investigate the metabolic pattern of FETO in vivo. Methods: In vitro assays were performed using different concentrations of MTO, ETO and FETO with constant concentrations of carboxylesterase. Human in vivo studies were performed with human blood samples drawn from the cubital vein. After sample clean-up, the serum was analysed by HPLC methods. Results: In vitro assays showed Michaelis-Menten constants of 115.1 µmol for FETO, 162.0 µmol for MTO and 168.6 µmol for ETO. Limiting velocities were 1.54 µmol/min (FETO), 1.47 µmol/min (MTO) and 1.35 µmol/min (ETO). This implies insignificantly decreased esterase stability of FETO compared with MTO and ETO. In vivo investigations showed a rapid metabolisation of FETO within the first 10 min (2 min: 91.41%±6.44%, n=6; 10 min: 23.78%±5.54%, n=4) followed by a smooth decrease in FETO from 20 to 90 min (20 min: 11.23%±3.79% n=4; 90 min: 3.68%±3.65%, n=4). Recovery rate was 61.43% ±3.19% (n=12). Conclusion: In vitro experiments demonstrated that FETO stability against esterases is comparable to that of ETO and MTO. The metabolic profile showed that FETO kinetics in humans are fast. [ABSTRACT FROM AUTHOR]

Purpose: Functional imaging of the adrenal cortex by means of PET may play an important clinical role. Recently, we presented the synthesis and first evaluation of a novel 11β-hydroxylase inhibitor, [18F] FETO, in rats displaying high tracer accumulation in the adrenals. In this study, we aimed to investigate for the first time the potency of [18F]FETO as a PET tracer for the adrenal cortex in humans. Methods: An average preparation yielded 1-2 GBq of [18F]FETO ready to use. Ten healthy volunteers aged 24-57 years (five male and five female) were included in the study. After i.v. administration of 365 MBq [18F] FETO (246-391 MBq), dynamic images were acquired in 2D standard mode in 14 frames over 45 min. Afterwards, whole-body scanning was performed. In addition to visual interpretation, semi-quantitative analysis using standardised uptake values (SUVs) was conducted. Results: [18F]FETO distribution was similar in all scanned volunteers. Visually, pronounced accumulation of [18F] FETO was found in the adrenals, whereas moderate uptake was observed—at least in some of the subjects—for liver, renal calices, gallbladder, stomach walls and pancreas. Kidney and bowels showed only faint uptake. Median SUVs for the right and left adrenal glands were 15.6 (10.0-28.6) and 15.7 (10.3-35.9), respectively. The reference tissue (liver) displayed a median SUV of 2.5 (2.2-4.6). Conclusion: [18F]FETO is a valuable tracer for adrenocortical PET imaging, combining the longer half-life of 18F with a high 11β-hydroxylase selectivity. In accordance with our findings in rats, FETO PET revealed very high accumulation in the adrenal glands in healthy volunteers. [ABSTRACT FROM AUTHOR]

Imaging of amino acid transport in brain tumours is more sensitive than fluorine-18 2-fluoro-deoxyglucose positron emission tomography (PET). The most frequently used tracer in this field is carbon-11 methionine (MET), which is unavailable for PET centres without a cyclotron because of its short half-life. The purpose of this study was to evaluate the performance of 3,4-dihydroxy-6-[[sup 18]F]fluoro-phenylalanine (FDOPA) in this setting, in comparison with MET. Twenty patients with known supratentorial brain lesions were referred for PET scans with FDOPA and MET. The diagnoses were 18 primary brain tumours, one metastasis and one non-neoplastic cerebral lesion. All 20 patients underwent PET with FDOPA (100 MBq, 20 min p.i.), and 19 of them also had PET scans with MET (800 MBq, 20 min p.i.). In all but one patient a histological diagnosis was available. In 15 subjects, histology was known from previous surgical interventions; in five of these patients, as well as in four previously untreated patients, histology was obtained after PET. In one untreated patient, confirmation of PET was possible solely by correlation with MRI; a histological diagnosis became available 10 months later. MET and FDOPA images matched in all patients and showed all lesions as hot spots with higher uptake than in the contralateral brain. Standardised uptake value ratios, tumour/contralateral side (mean±SD), were 2.05±0.91 for MET and 2.04±0.53 for FDOPA (NS). The benign lesion, which biopsy revealed to be a focal demyelination, was false positive, showing increased uptake of MET and FDOPA. We conclude that FDOPA is accurate as a surrogate for MET in imaging amino acid transport in malignant cerebral lesions for the purpose of visualisation of vital tumour tissue. It combines the good physical properties of [sup 18]F with the pharmacological properties of MET and might therefore be a valuable PET radiopharmaceutical in brain tumour imaging. [ABSTRACT FROM AUTHOR]

Examines the superiority of angiotensin converting enzyme (ACE) to angiotensin receptor blockade for renography in renal artery stenosis. Demonstration of renovascular hypertension by captopril renography; Performance of captopril, valsartan, and baseline renography; Evaluation of the alterations in renographic curves after intervention.

Abstract. About 15 years ago, iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging was introduced for the evaluation of myocardial sympathetic nerve function. Two uptake mechanisms for MIBG have so far been identified: uptake type I, a saturable, energy-dependent mechanism, and uptake type II, a non-saturable, energy-independent mechanism. We incubated isolated rabbit myocardial tissue samples with [sup 123]I-MIBG in order to assess the uptake characteristics and the influence of varying incubation conditions. Furthermore, we examined the effects of several drugs and uptake inhibitors on the myocardial uptake of MIBG. The in vitro myocardial uptake of MIBG reached a steady plateau at 23.87%+/-3.63% alter 1 h, i.e. a concentration gradient of 10, in a thermo-independent manner within a concentration range from 1.5 to 1500 micro M. This indicates an unsaturable uptake process in the tested concentrations. Preincubation with the following drugs caused a significant inhibitory effect on myocardial MIBG uptake: haloperidol, levomepromazine, metoprolol, labetalol and clomipramine. According to our findings, the uptake mechanism seems to be an unspecific process, but the concentration gradient of 10 makes passive diffusion unlikely. Further studies with uptake-II-blocking substances as well as with isolated myocardial cells will be needed to clarify the nature of the myocardial MIBG uptake mechanism. [ABSTRACT FROM AUTHOR]

Although active smoking is known to enhance platelet thromboxane production, no data on passive smoking are available yet. In an 18 m room, the influence of single and repeated exposure to passive smoke for 60 minutes was assessed in nonsmokers and smokers. Smokers and nonsmokers were matched for sex and age. All the evaluated parameters (plasma TXB, serum TXB, malondialdehyde, 11-dehydro-TXB, conversion of exogenous arachidonic acid to hydroxy-5,8,10-heptadecatrienoic acid, and TXB) were higher in smokers than nonsmokers at baseline conditions, immediately and 6 hours after passive exposure to cigarette smoke. Repeated exposure of nonsmokers rendered their platelets more activated, so they became closer to the behavior of smokers. Contributing to the development of hemostatic imbalance, these results indicate that passive smoking may enhance thromboxane A release from the platelets. [ABSTRACT FROM AUTHOR]