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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]

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: [ 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]

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]

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.