Clinical and histopathological findings hint at regional differences in the brain's sensitivity to metabolic changes in cirrhosis. The aim of the present study was to examine regional differences in cerebral ammonia metabolism in patients with cirrhosis and grade 0-to-I hepatic encephalopathy (HE). 13 N-ammonia, 15 O-water positron emission tomography (PET) and magnetic resonance imaging (MRI) were performed. Quantitative values of cerebral blood flow (CBF) and the initial cerebral ammonia uptake rate (K1) were derived for several regions of interest from images of the desired parameters after interactive coregistration with the patients' MRI-studies. CBF (mL/mL/min), K1 (mL/mL/min), and the ammonia extraction fraction (K1/CBF) showed marked regional variance with the highest levels in the thalamus, the lenticular nucleus, and the cerebellum. In conclusion, the regional differences in cerebral ammonia uptake correspond to the distribution of histopathological H epatic encephalopathy (HE) is characterized by distinct clinical findings: patients display motor disturbances even at the lower grades of HE. Patients' faces are without expression, their movements are very slow, and muscle tone may be rigid. In some patients, body position is similar to Parkinson's disease, and posture reflexes are abnormal. Several patients present with tremor or asterixis. 1 With regard to cognition, deficits in attention, visual perception, visuospatial orientation, and visual construction predominate. 2,3 Thus, clinical and neuropsychological findings hint at a special sensitivity of distinct cerebral regions for toxic substances active in HE. Recent 18 F-fluorodeoxyglucose PET studies of cerebral glucose metabolism in patients with cirrhosis and minimal encephalopathy support this assumption. It has been shown that in such patients with HE, glucose utilization is decreased in the cingulum and frontal and parieto-occipital cortex and increased in the basal ganglia, cerebellum, and temporomesial structures, compared to healthy controls and patients with cirrhosis and no HE. [4][5][6] The mechanisms responsible for these differences are unknown. Regional differences in ammonia metabolism could be one possible cause.Ammonia is regarded as playing a major role in the pathophysiology of HE. Recent studies have shown that hyperammonemia affects GABAergic and glutamatergic neurotransmission and induces astrocytic swelling, considered to be major pathophysiological mechanisms in the development of HE. [7][8][9] The aim of the present study was to analyze cerebral ammonia metabolism in patients with cirrhosis, examining regional differences and their relationship to the grade of encephalopathy and the grade of liver dysfunction.The results of this study have been presented, in part, in abstract form. 10 Patients and Methods

Visualisation of primary prostate cancer, its relapse and its metastases is a clinically relevant problem despite the availability of state-of-the-art methods such as CT, MRI, transrectal ultrasound and fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET). The aim of this study was to evaluate the efficacy of carbon-11 acetate and (18)F-FDG PET in the detection of prostate cancer and its metastases. Twenty-five patients were investigated during the follow-up of primary prostate cancer, suspected relapse or metastatic disease using (11)C-acetate PET; 15 of these patients were additionally investigated using (18)F-FDG PET. Fourteen patients were receiving anti-androgen treatment at the time of the investigation. Lesions were detected in 20/24 (83%) patients using (11)C-acetate PET and in 10/15 (75%) patients using (18)F-FDG PET. Based on the results of both PET scans, one patient was diagnosed with recurrent lung cancer. Median (18)F-FDG uptake exceeded that of (11)C-acetate in distant metastases (SUV =3.2 vs 2.3). However, in local recurrence and in regional lymph node metastases, (11)C-acetate uptake (median SUVs =2.9 and 3.8, respectively) was higher than that of (18)F-FDG (median SUVs =1.0 and 1.1, respectively). A positive correlation was observed between serum PSA level and both (11)C-acetate uptake and (18)F-FDG uptake. (11)C-acetate seems more useful than (18)F-FDG in the detection of local recurrences and regional lymph node metastases. (18)F-FDG, however, appears to be more accurate in visualising distant metastases. There may be a role for combined (11)C-acetate/(18)F-FDG PET in the follow-up of patients with prostate cancer and persisting or increasing PSA.

A method is presented to correct positron emission tomography (PET) data for head motion during data acquisition. The method is based on simultaneous acquisition of PET data in list mode and monitoring of the patient's head movements with a motion tracking system. According to the measured head motion, the line of response (LOR) of each single detected PET event is spatially transformed, resulting in a spatially fully corrected data set. The basic algorithm for spatial transformation of LORs is based on a number of assumptions which can lead to spatial artifacts and quantitative inaccuracies in the resulting images. These deficiencies are discussed, demonstrated and methods for improvement are presented. Using different kinds of phantoms the validity and accuracy of the correction method is tested and its applicability to human studies is demonstrated as well.

We studied quantitatively the effects of the discontinuity introduced in an otherwise homogeneous background by the cold walls of the standard spherical glass inserts commonly used in phantom measurements for calibration of threshold-based approaches to volumetric evaluation of PET investigations. We concentrated especially on the question of threshold-based volume determination. We computed analytically the convolution of an isotropic Gaussian point-spread function with the insert geometry (hot sphere + cold wall + warm background) and derived the theoretical background dependence of the volume reproducing threshold. This analysis shows a clear wall-related reduction of the optimal threshold with increasing background. The predictions of our theoretical analysis were verified in phantom measurements at background fractions between 0 and 0.29. Defining the background-corrected relative threshold [formula: see text] (T(abs): absolute volume reproducing threshold, A: measured activity at centre, B: background), we find that for a wall-less sphere T is independent of the background level. In the presence of cold walls, T drops (for not too small spheres, where recovery at the centre approaches 100%) from about 43% at B/A = 0 to about 25% at B/A = 0.5. Applying these thresholds to wall-less spheres leads to sizeable overestimates of the true volumes (43% at B/A = 0.5 for a sphere of 6 ml volume). We conclude that phantom measurements with standard sphere inserts for calibration of optimal thresholding algorithms introduce a systematic bias if performed at finite background levels. The observed background dependence is an artefact of the measurement procedure and does not reflect the conditions present in actual patient investigations.

In anthropomorphic software phantoms, the new method leads to promising results and to a clear improvement of volume delineation in comparison to conventional background-corrected thresholding. In the next step, the suitability for clinical routine will be further investigated.

Studies of resting regional cerebral glucose consumption (rCMRGlc) in nondemented patients with Parkinson's disease (PD) have produced conflicting results, reporting both reduced and normal metabolism in advanced disease and reduced or normal metabolism after dopaminergic therapy. To investigate these issues, [(18)F]fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed in 11 nondemented PD patients with advanced disease and 10 age-matched controls. PD patients were studied after withdrawal of all dopaminergic medication to produce a practically defined off condition, and a second time 1 hour after levodopa, resulting in a clinical on state. Dynamic PET scans and simultaneous arterialised venous blood samples of [(18)F] activity were obtained. A graphical approach was used to generate parametric images of rCMRGlc and statistical parametric mapping to localise significant metabolic changes in PD. Compared with controls, global rCMRGlc was reduced in the on but not in the off condition in PD. In both states, significant regional reductions of glucose uptake were found in the parietal, frontal, temporal cortex, and caudate nucleus. Reductions correlated with the severity of disability in frontal and temporal cortex. Direct comparison between on and off conditions revealed relatively greater reductions of uptake in the ventral/orbital frontal cortex and the thalamus during on. Results suggest that cortical and caudate hypometabolism are common in advanced PD and that caution is mandatory if [(18)F]FDG PET is being used to differentiate advanced PD from dementia and progressive supranuclear palsy where similar reductions are seen. Furthermore, in PD, administration of levodopa is associated with further hypometabolism in orbitofrontal cortex; an area known to be relevant for reversal learning where performance is typically impaired after dopaminergic treatment.

Despite ongoing efforts to develop new treatment options, the prognosis for patients with inoperable esophageal carcinoma is still poor and the reliability of individual therapy outcome prediction based on clinical parameters is not convincing. The aim of this work was to investigate whether PET can provide independent prognostic information in such a patient group and whether the tumor-toblood standardized uptake ratio (SUR) can improve the prognostic value of tracer uptake values. Methods: 18 F-FDG PET/CT was performed in 130 consecutive patients (mean age ± SD, 63 ± 11 y; 113 men, 17 women) with newly diagnosed esophageal cancer before definitive radiochemotherapy. In the PET images, the metabolically active tumor volume (MTV) of the primary tumor was delineated with an adaptive threshold method. The blood standardized uptake value (SUV) was determined by manually delineating the aorta in the low-dose CT. SUR values were computed as the ratio of tumor SUV and blood SUV. Uptake values were scan-time-corrected to 60 min after injection. Univariate Cox regression and Kaplan-Meier analysis with respect to overall survival (OS), distant metastases-free survival (DM), and locoregional tumor control (LRC) was performed. Additionally, a multivariate Cox regression including clinically relevant parameters was performed. Results: In multivariate Cox regression with respect to OS, including T stage, N stage, and smoking state, MTV-and SUR-based parameters were significant prognostic factors for OS with similar effect size. Multivariate analysis with respect to DM revealed smoking state, MTV, and all SUR-based parameters as significant prognostic factors. The highest hazard ratios (HRs) were found for scan-time-corrected maximum SUR (HR 5 3.9) and mean SUR (HR 5 4.4). None of the PET parameters was associated with LRC. Univariate Cox regression with respect to LRC revealed a significant effect only for N stage greater than 0 (P 5 0.048). Conclusion: PET provides independent prognostic information for OS and DM but not for LRC in patients with locally advanced esophageal carcinoma treated with definitive radiochemotherapy in addition to clinical parameters. Among the investigated uptake-based parameters, only SUR was an independent prognostic factor for OS and DM. These results suggest that the prognostic value of tracer uptake can be improved when characterized by SUR instead of SUV. Further investigations are required to confirm these preliminary results.

The intentional binding of radioligands to albumin gains increasing attention in the context of radiopharmaceutical cancer therapy as it can lead to an enhanced radioactivity uptake into the tumor lesions and, thus, to a potentially improved therapeutic outcome. However, the influence of the radioligand’s albumin-binding affinity on the time profile of tumor uptake has been only partly addressed so far. Based on the previously identified N ε-4-(4-iodophenyl)­butanoyl-lysine scaffold, we designed “clickable” lysine-derived albumin binders (cLABs) and determined their dissociation constants toward albumin by novel assay methods. Structure–activity relationships were derived, and selected cLABs were applied for the modification of the somatostatin receptor subtype 2 ligand (Tyr3)­octreotate. These novel conjugates were radiolabeled with copper-64 and subjected to a detailed in vitro and in vivo radiopharmacological characterization. Overall, the results of this study provide an incentive for further investigations of albumin binders for applications in endoradionuclide therapies.