PSA and PSA Kinetics Thresholds for the Presence of 68Ga-PSMA-11 PET/CT-Detectable Lesions in Patients with Biochemical Recurrent Prostate Cancer

68Ga-PSMA-11 positron-emission tomography/computed tomography (PET/CT) is commonly used for restaging recurrent prostate cancer (PC) in European clinical practice. The goal of this study is to determine the optimum time for performing these PET/CT scans in a large cohort of patients by identifying the prostate-specific-antigen (PSA) and PSA kinetics thresholds for detecting and localizing recurrent PC. This retrospective analysis includes 581 patients with biochemical recurrence (BC) by definition. The performance of 68Ga-PSMA-11 PET/CT in relation to the PSA value at the scan time as well as PSA kinetics was assessed by the receiver-operating-characteristic-curve (ROC) generated by plottin…

Predicting the in vivo release from a liposomal formulation by IVIVC and non-invasive positron emission tomography imaging

This study aimed to predict the in vivo performance from the in vitro release of a low-molecular weight model compound, [(18)F]-2-fluoro-2-deoxy-d-glucose ([(18)F]FDG), from liposomes and by means of positron emission tomography (PET). Liposomes composed of hydrogenated phosphatidylcholine (HPC) were prepared by a freeze-thaw method. Particle size distribution was measured by dynamic light scattering (DLS). In vitro release was examined with a dispersion method detecting the radioactivity of [(18)F]FDG. In vivo release of [(18)F]FDG, following i.p. injection of the liposomes in rats, was determined by using a Micro-PET scanner. Convolution was performed to predict the in vivo profiles from …

Choice of reference area in studies of Alzheimer's disease using positron emission tomography with fluorodeoxyglucose-F18

At present, there is still no consensus on the choice of the reference area in positron emission tomography (PET) studies of Alzheimer's disease (AD). In this study, PET scans with fluorodeoxyglucose-F18 were carried out in the following groups of subjects: 47 patients with probable AD, 8 patients with mild cognitive impairment, and 15 age-similar healthy subjects. Scans normalized to the cerebral global mean (CGM), cerebellum (CBL), and the primary sensorimotor cortex (SMC). We evaluated the effect of the different count normalization procedures on the accuracy of (18)F-FDG PET to detect AD-specific metabolic abnormalities (voxel-based group comparison) and to differentiate between patient…

Noninvasive assessment of Crohn's disease activity: a comparison of 18F-fluorodeoxyglucose positron emission tomography, hydromagnetic resonance imaging, and granulocyte scintigraphy with labeled antibodies.

Detection of disease activity in Crohn's disease (CD) is of crucial importance for diagnosis and management of the disease. Noninvasive methods for monitoring are desirable and comprise hydromagnetic resonance imaging (hydro-MRI) and leukocyte scintigraphy. In addition, a recent case report indicated the potential of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to assess CD activity. However, comparative prospective studies are lacking.Between February, 1999 and August, 2000, 59 patients with CD were enrolled in a prospective study to assess disease activity by FDG-PET, hydro-MRI, and immunoscintigraphy with anti-nonspecific cross-reacting antigen 95 antigranulocyte antibod…

Metabolic and structural connectivity within the default mode network relates to working memory performance in young healthy adults.

Abstract Studies of functional connectivity suggest that the default mode network (DMN) might be relevant for cognitive functions. Here, we examined metabolic and structural connectivity between major DMN nodes, the posterior cingulate (PCC) and medial prefrontal cortex (MPFC), in relation to normal working memory (WM). DMN was captured using independent component analysis of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) data from 35 young healthy adults (27.1 ± 5.1 years). Metabolic connectivity, a correlation between FDG uptake in PCC and MPFC, was examined in groups of subjects with (relative to median) low (n = 18) and high (n = 17) performance on digit span backward te…

Correlation of cognition and FDG-PET findings in early multiple sclerosis

Introduction: Patients with multiple sclerosis (MS), disease history of 11.5 years, an expanded disability status scale (EDSS) up to 6.0 and an involvement of verbal and/or spatial and long-term memory showed a bilateral reduction of glucose metabolism in the cingulate gyrus, thalamus, associative occipital cortex and cerebellum. To our knowledge no similar studies in early stages of MS are reported. Therefore we stressed the question of possible correlation of quality of life, objective cognitive impairment and FDG-PET findings in newly diagnosed definite MS according to McDonald criteria. Methods: In 11 patients (f=4, m=7, mean age: 35 years (CI 25–42), IQ 112 (CI 97–118)) with newly diag…

Decreased dopamine D2/D3-receptor binding in temporal lobe epilepsy: an [18F]fallypride PET study.

Summary: Purpose: Although animal data are suggestive, evidence for an alteration of the extrastriatal dopaminergic system in human focal epilepsy is missing. Methods: To quantify D2/D3-receptor density, we studied seven patients with temporal lobe epilepsy (TLE) and nine agematched controls with positron emission tomography (PET) by using the high-affinity dopamine D2/D3-receptor ligand [ 18 F]Fallypride ([ 18 F]FP) suitable for imaging extrastriatal binding. TLE was defined by interictal and ictal video-EEG, magnetic resonance imaging (MRI), and [ 18 F]fluorodeoxyglucose ([ 18 F]FDG)-PET and was due to hippocampal sclerosis (HS), based on histology in all patients. Primary analysis was ba…

SPECT-Untersuchungen mit dem 123I-markierten Dopamintransporter-Liganden FP-CIT (DaTSCANTM)

ZusammenfassungDie S1-Leitlinie soll bei der Indikationsstellung, Durchführung, Interpretation und Befundung von SPECT-Untersuchungen des Dopamintransporters (DAT) mit DaTSCANTM unterstützen. Gegenüber der Vorgängerversion von 2007 berücksichtigt die vorliegende Aktualisierung und Überarbeitung die neuere wissenschaftliche Literatur, zwischenzeitlich veröffentlichte Guidelines der europäischen (EANM) und amerikanischen Fachgesellschaften (SNM), sowie die aktuelle Fassung der S3-Leitlinie „Idiopathisches Parkinson-Syndrom“ der Deutschen Gesellschaft für Neurologie. Zudem finden neue technische Möglichkeiten Berücksichtigung.

Prognostic Factors Determining Long-Term Survival in Well-Differentiated Thyroid Cancer: An Analysis of Four Hundred Eighty-Four Patients Undergoing Therapy and Aftercare at the Same Institution

Identification of the prognostic factors relevant for long-term survival in differentiated thyroid cancer in a homogenously treated patient cohort in order to allow a better initial risk stratification.Four hundred eighty-four (358 females/126 males) patients with differentiated thyroid cancer (330 papillary [68.2%]; 154 follicular [31.8%]) were included. Inclusion criteria consisted of treatment with a uniform therapy scheme and continuous aftercare in the same institution. Initial diagnosis was between 1975-1995 (age at diagnosis, 14-84 years, median, 49.7). Tumor stage: pT1, n = 92; pT2, 211; pT3, 58; pT4, 123. Low-risk:or=pT3 NX M0, 331; high-risk pT4 and/or M1, 153. After thyroidectomy…

Impact of prompt gamma emission of 44Sc on quantification in preclinical and clinical PET systems

Abstract 44Sc is an increasingly investigated positron emitter for use in positron emission tomography (PET) imaging. However, 44Sc is a non-pure positron emitter, since prompt photons are co-emitted during the decay process. This study investigates coincidence energy spectra of 44Sc and its impact on PET quantification on a preclinical and clinical PET system in comparison with 18F. The raw data of the coincidence events revealed characteristic differences comparing the photon energy distribution of 44Sc and 18F. Due to prompt gamma emission of 44Sc, activity recovery is underestimated on PET systems. However, clinical PET imaging of 44Sc with acceptable quantitative accuracy appears feasi…

The striatal and extrastriatal D2/D3 receptor-binding profile of clozapine in patients with schizophrenia.

Positron emission tomography (PET) studies reveal that clozapine at clinically used doses occupies less than 60% of D2/D3 dopamine receptors in human striatum. Here, the occupancy of D2/D3 dopamine receptors by clozapine in patients with schizophrenia was determined to test the hypothesis that clozapine binds preferentially to extrastriatal dopamine receptors. A total of 15 clozapine-treated inpatients with schizophrenia underwent a [18F]fallypride PET scan. Receptor occupancy was calculated as percent reduction in binding potential relative to unblocked values measured in seven normal volunteers. Mean D2/D3 receptor occupancy was statistically significantly higher in cortical (inferior tem…

Prospective Evaluation of Positron Emission Tomography in the Preoperative Staging of Esophageal Carcinoma

Hypothesis Positron emission tomography (PET) is a useful tool in the selection of patients with esophageal cancer who may not benefit from esophageal resection. Design Case series. Setting Tertiary care hospital. Patients Eighty-one patients with newly diagnosed esophageal cancer who underwent PET and computer tomography (CT) of the chest and abdomen (and of the neck in 45 patients) within 45 days were included. Main Outcome Measures We calculated the sensitivity and specificity in detecting metastatic sites on the basis of 31 histologically verified lesions. In addition to results obtained on CT, the information provided by PET was evaluated with a view to the choice of management strateg…

Basal opioid receptor binding is associated with differences in sensory perception in healthy human subjects: a [18F]diprenorphine PET study.

The endogenous opioid system is involved in many body functions including pain processing and analgesia. To determine the role of basal opioid receptor availability in the brain in pain perception, twenty-three healthy subjects underwent positron emission tomography (PET) utilizing the subtype-nonselective opioid antagonist [(18)F]diprenorphine, quantitative sensory testing (QST) and the cold pressor test. Binding potentials (BPs) were calculated using a non-invasive reference tissue model and statistical parametric mapping was applied for t-statistical analysis on a voxelwise basis. We found that cold pain-sensitive subjects present a significantly lower BP in regions including the bilater…

Metabolic connectivity as index of verbal working memory

Positron emission tomography (PET) data are commonly analyzed in terms of regional intensity, while covariant information is not taken into account. Here, we searched for network correlates of healthy cognitive function in resting state PET data. PET with [18F]-fluorodeoxyglucose and a test of verbal working memory (WM) were administered to 35 young healthy adults. Metabolic connectivity was modeled at a group level using sparse inverse covariance estimation. Among 13 WM-relevant Brodmann areas (BAs), 6 appeared to be robustly connected. Connectivity within this network was significantly stronger in subjects with above-median WM performance. In respect to regional intensity, i.e., metaboli…

The Impact of 68Ga-PSMA PET/CT and PET/MRI on the Management of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a transmembrane protein with significantly increased expression in the cells and metastases of prostate carcinoma (CaP). PSMA-expression correlates with higher serum levels of prostate-specific antigen (PSA) and a higher Gleason score (GS). This finding has led to the development of novel imaging modalities such as 68Ga-/18F-labeled PSMA positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MRI). This article reviews the literature pertaining to various new imaging technologies for the management of CaP. PSMA positron emission tomography/computed tomography appears to be an exce…

Quantification of the Cannabinoid Type 1 Receptor Availability in the Mouse Brain

Introduction: The endocannabinoid system is involved in several diseases such as addictive disorders, schizophrenia, post-traumatic stress disorder, and eating disorders. As often mice are used as the preferred animal model in translational research, in particular when using genetically modified mice, this study aimed to provide a systematic analysis of in vivo cannabinoid type 1 (CB1) receptor ligand-binding capacity using positron emission tomography (PET) using the ligand [18F]MK-9470. We then compared the PET results with literature data from immunohistochemistry (IHC) to review the consistency between ex vivo protein expression and in vivo ligand binding.Methods: Six male C57BL/6J (6–9…

In vivo imaging of dopamine receptors in a model of temporal lobe epilepsy

Alterations in dopamine neurotransmission in animal models of epilepsies have been frequently demonstrated using invasive neuroscience or ex vivo techniques. We aimed to test whether corresponding alterations could be detected by noninvasive in vivo brain imaging with positron emission tomography (PET) in the chronic phase of the rat pilocarpine model of temporal lobe epilepsy.Six pilocarpine-treated Wistar rats exhibiting spontaneous recurrent seizures and nine control rats were studied with PET using [(18)F]-fallypride, a high-affinity dopamine D(2/3) receptor ligand. Parametric images of [(18)F]-fallypride specific binding were calculated using a reference tissue method, and the two grou…

Demonstration of retinal afferents in the RCS rat, with reference to the retinohypothalamic projection and suprachiasmatic nucleus.

In the Royal College of Surgeons (RCS) rat, characterized by inherited retinal dystrophy, retinal projections to the brain were studied using anterograde neuronal transport of cholera toxin B subunit upon injection into one eye. The respective immunoreactivity was found predominantly contralateral to the injection site in the lateral geniculate nucleus, superior colliculus, nucleus of the optic tract, medial terminal nucleus of the accessory optic tract, and bilateral hypothalamic suprachiasmatic nuclei. Although terminal density was somewhat reduced in dystrophic rats, the projection patterns in these animals appeared similar to those seen in their congenic controls and were comparable to …

Stage-dependent agreement between cerebrospinal fluid proteins and FDG-PET findings in Alzheimer's disease.

Cerebral hypometabolism and abnormal levels of amyloid beta (Aβ), total (t-tau) and phosphorylated tau (ptau) proteins in cerebrospinal fluid (CSF) are established biomarkers of Alzheimer's disease (AD). We examined the agreement between these biomarkers in a single center study of patients with AD of severity extending over a wide range. Forty seven patients (MMSE 21.4 ± 3.6, range 13-28 points) with incipient and probable AD underwent positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) and lumbar puncture for CSF assays of Aβ1-42, p-tau181, and t-tau. All findings were classified as either positive or negative for AD. Statistical analyses were performed for the whole samp…

Antiamphiphysin-positive stiff-person syndrome associated with small cell lung cancer

The paraneoplastic amphiphysin(+) stiff-person syndrome (SPS) has so far only been described in women with breast adenocarcinoma. Here, we describe the rare case of a female patient with antiamphiphysin(+) SPS due to small cell cancer of the lung.

Anterior limbic alpha-like activity: a low resolution electromagnetic tomography study with lorazepam challenge

Summary Objective To verify findings of an independently regulated anterior limbic alpha band source. Methods In a randomised cross-over study, the spontaneous EEG was recorded in nine healthy subjects after i.v. lorazepam or placebo. Intracerebral current densities within classical frequency bands were estimated with low resolution electromagnetic tomography [LORETA] and compared between groups with t -statistical parametric mapping [SPM{ t }]. A region-of-interest [ROI] based method was used to compare frontal and occipital alpha band activity changes. Results Irrespective of treatment group, local maxima of alpha band power were localised both in the occipital lobe, Brodman area [BA] 18,…

High opiate receptor binding potential in the human lateral pain system

To determine how opiate receptor distribution is co-localized with the distribution of nociceptive areas in the human brain, eleven male healthy volunteers underwent one PET scan with the subtype-nonselective opioidergic radioligand [(18)F]fluoroethyl-diprenorphine under resting conditions. The binding potential (BP), a parameter for the regional cerebral opioid receptor availability, was computed using the occipital cortex as reference region. The following regions of interest (ROIs) were defined on individual MR images: thalamus, sensory motor strip (SI/MI area), frontal operculum, parietal operculum, anterior insular cortex, posterior insular cortex, anterior cingulate cortex (ACC; peri-…

Toll like receptor mediated immune stimulation can be visualized in vivo by [ 18 F]FDG-PET

Abstract Introduction High uptake of [ 18 F]-2-fluorodeoxyglucose ([ 18 F]FDG) by inflammatory cells is a frequent cause of false positive results in [ 18 F]FDG-positron-emission tomography (PET) for cancer diagnostics. Similar to cancer cells, immune cells undergo significant increases in glucose utilization following activation, e.g., in infectious diseases or after vaccination during cancer therapy. The aim of this study was to quantify certain immune effects in vitro and in vivo by [ 18 F]FDG-PET after stimulation with TLR ligands and specific antibodies. Methods In vivo [ 18 F]FDG-PET/magnetic resonance imaging (MRI) and biodistribution was performed with C57BL/6 mice immunized with Cp…

Positronen-Emissions-Tomographie zum präoperativen Staging des Ösophaguskarzinoms

BACKGROUND AND OBJECTIVE Exact preoperative staging is a prerequisite for the indication as well as the choice of the appropriate operative technique for patients with esophageal carcinoma. In this prospective study we assessed whether positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG) increases the accuracy of staging compared to standard computer tomography (CT) and leads to a different therapeutic approach. PATIENTS AND METHODS 30 patients (25 men, 5 women, median age 63 years) with histologically identified carcinoma of the esophagus (n =29) and the cardia (n = 1), respectively, were studied. All patients underwent FDG-PET imaging of the neck, chest, and abdomen as w…

Peptide Receptor Radionuclide Therapy Combined With Chemotherapy in Patients With Neuroendocrine Tumors

Combinations of therapies may enhance therapeutic effects without significantly increasing the incidence of adverse events. However, there are few data regarding survival after concomitant chemotherapy and peptide receptor radionuclide therapy (PRRT) with [Lu]Lu-octreotate in patients with neuroendocrine tumors (NETs). Thus, we explored the outcome of this combination of therapies.Fifteen patients with somatostatin receptor-positive, rapidly progressive G2/G3 NETs during chemotherapy or PRRT alone from 2 German cancer centers were included in the retrospective analysis. The patients received a combination of PRRT and chemotherapy with temozolomide (n = 3) or temozolomide plus capecitabine (…

Acute effect of intravenously applied alcohol in the human striatal and extrastriatal D2 /D3 dopamine system

Investigations on the acute effects of alcohol in the human mesolimbic dopamine D2 /D3 receptor system have yielded conflicting results. With respect to the effects of alcohol on extrastriatal D2 /D3 dopamine receptors no investigations have been reported yet. Therefore we applied PET imaging using the postsynaptic dopamine D2 /D3 receptor ligand [18 F]fallypride addressing the question, whether intravenously applied alcohol stimulates the extrastriatal and striatal dopamine system. We measured subjective effects of alcohol and made correlation analyses with the striatal and extrastriatal D2 /D3 binding potential. Twenty-four healthy male μ-opioid receptor (OPRM1)118G allele carriers underw…

Hybrid Chelator-Based PSMA Radiopharmaceuticals: Translational Approach

(1) Background: Prostate-specific membrane antigen (PSMA) has been extensively studied in the last decade. It became a promising biological target in the diagnosis and therapy of PSMA-expressing cancer diseases. Although there are several radiolabeled PSMA inhibitors available, the search for new compounds with improved pharmacokinetic properties and simplified synthesis is still ongoing. In this study, we developed PSMA ligands with two different hybrid chelators and a modified linker. Both compounds have displayed a promising pharmacokinetic profile. (2) Methods: DATA5m.SA.KuE and AAZTA5.SA.KuE were synthesized. DATA5m.SA.KuE was labeled with gallium-68 and radiochemical yields of various…

Opioid receptor PET reveals the psychobiologic correlates of reward processing.

Little is known about the neurobiologic correlates of human personality. On the basis of the key role of the central opioidergic system in addiction and substance abuse, we investigated the relationship between certain personality traits that are supposed to be relevant in addiction and the opioid receptor status in healthy subjects.We investigated 23 healthy male volunteers who were extensively clinically tested to exclude substance abuse. All of the subjects underwent 1 PET scan with the subtype-nonselective opioidergic radioligand 18F-fluoroethyl-diprenorphine under resting conditions without sensory or cognitive stimulation. Subsequently, the subjects were psychologically tested for the…

Functional Plasticity after Unilateral Vestibular Midbrain Infarction in Human Positron Emission Tomography.

The aim of the study was to uncover mechanisms of central compensation of vestibular function at brainstem, cerebellar, and cortical levels in patients with acute unilateral midbrain infarctions presenting with an acute vestibular tone imbalance. Eight out of 17 patients with unilateral midbrain infarctions were selected on the basis of signs of a vestibular tone imbalance, e.g., graviceptive (tilts of perceived verticality) and oculomotor dysfunction (skew deviation, ocular torsion) in F18-fluordeoxyglucose (FDG)-PET at two time points: A) in the acute stage, and B) after recovery 6 months later. Lesion-behavior mapping analyses with MRI verified the exact structural lesion sites. Group su…

Enhanced Functional Activity of the Cannabinoid Type-1 Receptor Mediates Adolescent Behavior.

Adolescence is characterized by drastic behavioral adaptations and comprises a particularly vulnerable period for the emergence of various psychiatric disorders. Growing evidence reveals that the pathophysiology of these disorders might derive from aberrations of normal neurodevelopmental changes in the adolescent brain. Understanding the molecular underpinnings of adolescent behavior is therefore critical for understanding the origin of psychopathology, but the molecular mechanisms that trigger adolescent behavior are unknown. Here, we hypothesize that the cannabinoid type-1 receptor (CB1R) may play a critical role in mediating adolescent behavior because enhanced endocannabinoid (eCB) sig…

Head and neck paragangliomas: Report of 175 patients (1989-2010)

Attention of the otorhinolaryngologist needs to be drawn to the versatile aspects of head and neck paragangliomas (PGLs).This study is a retrospective, nonrandomized clinical study of all 175 individuals with PGLs treated in our department between 1989 and 2010. A genetic analysis was performed on 86 patients.The 175 patients presented 224 head and neck PGLs as well as 2 thyroid papillary carcinomas. Genetic analysis resulted in 1 patient positive for a von Hippel-Lindau (VHL) gene mutation and 34 for succinate dehydrogenase (SDH) gene mutations (22 SDHD, 7 SDHC, and 5 SDHB), 12 of the latter carrying a novel mutation. Thirty-three patients (18.9%) had multiple PGLs and 11 patients (6.3%) h…

Pharmacokinetics of the cannabinoid receptor ligand [18 F]MK-9470 in the rat brain - Evaluation of models using microPET

PURPOSE The positron emission tomography ligand [18 F]MK-9470 is an inverse agonist that binds reversibly and with high affinity to the cannabinoid type 1 receptor. Due to its slow brain kinetics, care is required in the definition of its dissociation rates from the receptor. The goal of this study was to investigate pharmacokinetic analysis methods using an arterial input function. METHODS Five Sprague-Dawley rats received injections of 13 to 25 MBq of [18 F]MK-9470 and were scanned over a period of 90 min. Arterial blood samples were collected throughout the scan. Data were analyzed using four different compartmental models: a reversible one-tissue model, reversible two tissue models with…

Reply: “The Impact of 68Ga-PSMA PET/CT and PET/MRI on the Management of Prostate Cancer”

Evaluation of MRI and cannabinoid type 1 receptor PET templates constructed using DARTEL for spatial normalization of rat brains

Purpose: Image registration is one prerequisite for the analysis of brain regions in magnetic-resonance-imaging (MRI) or positron-emission-tomography (PET) studies. Diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) is a nonlinear, diffeomorphic algorithm for image registration and construction of image templates. The goal of this small animal study was (1) the evaluation of a MRI and calculation of several cannabinoid type 1 (CB1) receptor PET templates constructed using DARTEL and (2) the analysis of the image registration accuracy of MR and PET images to their DARTEL templates with reference to analytical and iterative PET reconstruction algorithms. Methods:…

Modeling Vestibular Compensation: Neural Plasticity Upon Thalamic Lesion.

The present study in rats was conducted to identify brain regions affected by the interruption of vestibular transmission and to explore selected aspects of their functional connections. We analyzed, by positron emission tomography (PET), the regional cerebral glucose metabolism (rCGM) of cortical, and subcortical cerebral regions processing vestibular signals after an experimental lesion of the left laterodorsal thalamic nucleus, a relay station for vestibular input en route to the cortical circuitry. PET scans upon galvanic vestibular stimulation (GVS) were conducted in each animal prior to lesion and at post-lesion days (PLD) 1, 3, 7, and 20, and voxel-wise statistical analysis of rCGM a…

Positron Emission Tomography for Staging Esophageal Cancer: Does It Lead to a Different Therapeutic Approach?

Accurate preoperative staging is essential for the indication and selection of the appropriate surgical procedure in patients with esophageal cancer. The present prospective study was designed to determine if the preoperative use of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) increases the accuracy of staging esophageal cancer compared with computed tomography (CT) and if it thereby leads to a different therapeutic approach. A total of 58 patients, 46 men and 12 women (mean age 61 years), with histologic proof of esophageal carcinoma underwent FDG-PET of the neck, chest, and abdomen, as well as CT of the chest and abdomen, to determine tumor stage. FDG-PET and CT data we…

Is the chromanol head group of vitamin E nature's final truth on chain-breaking antioxidants?

AbstractTocopherol is believed to be the most potent naturally occurring chain-breaking antioxidant. Hence, its refined phenolic head group chromanol may represent an optimum evolutionary solution to the problem of free-radical chain reactions in the lipid bilayer. To test the universal validity of this assumption beyond phenolic head groups, we have synthesized aromatic amine analogues of vitamin E and trolox with otherwise closely matching physicochemical properties: NH-toc and NH-trox. We have found that NH-toc and NH-trox were significantly more potent free radical scavengers, lipid peroxidation inhibitors and cytoprotective agents than their phenolic templates, tocopherol and trolox. I…

SPM-based count normalization provides excellent discrimination of mild Alzheimer's disease and amnestic mild cognitive impairment from healthy aging☆

Statistical comparisons of [(18)F]FDG PET scans between healthy subjects and patients with Alzheimer's disease (AD) or amnestic mild cognitive impairment (aMCI) using Statistical Parametric Mapping (SPM) usually require normalization of regional tracer uptake via ROIs defined using additional software. Here, we validate a simple SPM-based method for count normalization. FDG PET scans of 21 mild, 15 very mild AD, 11 aMCI patients and 15 age-matched controls were analyzed. First, we obtained relative increases in the whole patient sample compared to controls (i.e. areas relatively preserved in patients) with proportional scaling to the cerebral global mean (CGM). Next, average absolute counts…

Net influx of plasma 6-[18F]fluoro-L-DOPA (FDOPA) to the ventral striatum correlates with prefrontal processing of affective stimuli.

Dopaminergic neurotransmission in the ventral and dorsal striatum interact with central processing of rewarding and reward-indicating stimuli, and may affect frontocortical-striatal-thalamic circuits regulating goal-directed behaviour. Thirteen healthy male volunteers were investigated with multimodal imaging, using the radioligand 6-[ 18 F]fluoro-L-DOPA (FDOPA) for positron emission tomography (PET) measurements of dopamine synthesis capacity, and also functional magnetic resonance imaging (fMRI) in a cognitive activation paradigm. We calculated the correlation between FDOPA net blood-brain influx (K app in ; ml/g/min) in the ventral and associative dorsal striatum and BOLD signal changes …

Reduced Cerebral Fluoro-l-Dopamine Uptake in Adult Patients Suffering from Phenylketonuria

Deficiency of phenylalanine hydroxylase activity in phenylketonuria (PKU) causes an excess of phenylalanine (Phe) throughout the body, predicting impaired synthesis of catecholamines in the brain. To test this hypothesis, we used positron emission tomography (PET) to measure the utilization of 6-[18F]fluoro-l-dopamine (FDOPA) in the brain of adult patients suffering from PKU and in healthy controls. Dynamic 2-h long FDOPA emission recordings were obtained in seven adult PKU patients (five females, two males; age: 21 to 27 years) with elevated serum Phe levels, but lacking neurologic deficits. Seven age-matched, healthy volunteers were imaged under identical conditions. The utilization of F…

Die Positronenemissionstomographie zur pr�operativen Lymphknotendiagnostik bei �sophaguskarzinom

Vorraussetzung fur Indikation und Wahl des geeigneten operativen Verfahrens bei Patienten mit Osophaguskarzinom ist ein genaues praoperatives Staging. Ziel der prospektiven Studie war es, zu klaren, ob eine Positronenemissionstomographie mit 18F-Fluoro-Deoxyglukose (FDG-PET) die Genauigkeit des praoperativen Lymphknotendiagnostik gegenuber der Computertomographie (CT) erhoht und die Wahl des operativen Zugangs zur Osophagusresektion beeinflusst. 58 Patienten, 46 Manner und 12 Frauen (Alter 61 Jahre im Mittel), erhielten bei histologisch gesichertem Osophaguskarzinom im Rahmen des Stagings ein FDG-PET von Hals, Thorax und Abdomen sowie ein CT von Thorax und Abdomen. Sensitivitat, Spezifitat …

Alteration of dopamine D2/D3 receptor binding in patients with juvenile myoclonic epilepsy

Summary Purpose:  To quantify extrastriatal and striatal D2/D3 receptor binding in patients with juvenile myoclonic epilepsy (JME) using the high-affinity dopamine D2/D3 receptor positron emission tomography (PET) ligand 18F-Fallypride ([18F]FP). Methods:  Twelve patients with JME and 21 age-matched control subjects were studied. Dynamic images (180 min) were acquired after injection of [18F]FP. Patients had been seizure-free of all seizure types for at least 10 days before scanning. Parametric images of binding potential (BP) were created using the simplified reference tissue model. The images were stereotactically normalized using a ligand-specific template. We performed a voxel-based ana…

An approach to the evaluation of the activity of the DNA repair enzyme O6-methylguanine-DNA-methyl-transferase in tumor tissue in vivo: syntheses of 6-benzyloxy-9-(2-[18F]fluoroethyl)-9H-purin-2-yl-amine and 6-benzyloxy-7-(2-[18F]fluoroethyl)-7H-purin-2-yl-amine

Abstract The resistance of tumor cells to the cytostatic activity of methylating and chloroethylating anticancer drugs is determined by the level of expression of the DNA repair protein O 6 -methylguanine-DNA-methyl-transferase (MGMT). The synthesis of labelled 6-benzyloxy-9H-purin-2-ylamine derivatives should hence allow a quantification of the MGMT status of tumor and non-target tissue in vivo. 6-benzyloxy-9-(2-fluoroethyl)-9H-purin-2-yl-amine and 6-benzyloxy-7-(2-fluoroethyl)-7H-purin-2-yl-amine were synthesized and evaluated in vitro, both showing an affinity of 1.8 μM. 6-benzyloxy-9-(2-[ 18 F]fluoroethyl)-9H-purin-2-yl-amine and 6-benzyloxy-7-(2-[ 18 F]fluoroethyl)-7H-purin-2-yl-amine …

In Vivo Molecular Imaging of Somatostatin Receptors in Pancreatic Islet Cells and Neuroendocrine Tumors by Miniaturized Confocal Laser-Scanning Fluorescence Microscopy

The aim of the study was to evaluate real time in vivo molecular imaging of somatostatin receptors (sstrs) using a handheld miniaturized confocal laser scan microscope (CLM) in conjunction with fluorescein-labeled octreotate (OcF) in healthy mice and murine models of neuroendocrine tumors. For CLM a small rigid probe (diameter 7 mm) with an integrated single line laser (488 nm) was used (optical slice thickness 7 μm; lateral resolution 0.7 μm). OcF was synthesized via Fmoc solid-phase peptide synthesis and purified by HPLC showing high-affinity binding to the sstr2 (IC50 6.2 nmol). For in vitro evaluation, rat and human pancreatic cancer cells were used and characterized with respect to its…

Acute Alcohol Effects on Neuronal and Attentional Processing: Striatal Reward System and Inhibitory Sensory Interactions under Acute Ethanol Challenge

The acute influence of ethanol on cerebral activity induces complex psycho-physiological effects that are considerably more pronounced during acute ethanol influx than during maximal blood alcohol concentration (elimination phase). Despite the psychiatric and forensic relevance of these different ethanol effects, the underlying neuronal mechanisms are still unclear. In total, 20 male healthy volunteers were investigated each with three different experimental conditions in a randomized order using an intravenous ethanol challenge (40 g bolus infusion): during influx phase, elimination phase, and under placebo condition. During and after the ethanol (or placebo) infusion, neuropsychological t…

Using mRNA and small RNA gene expression changes in peripheral blood for easy detection of Ra-223 incorporation

Diagnostic Performance of 68Ga-PSMA-11 Positron-emission-tomography/Computed-tomography in a Large Cohort of Patients with Biochemical Recurrence of Prostate Carcinoma.

Gallium-68 (Ga) prostate-specific-membrane-antigen positron-emission-tomography/computed-tomography is a highly promising method for imaging primary and recurrent prostate cancer. These dual-modality imaging technologies enable whole-body functional and anatomical evaluation in a single session. This study investigated the performance of Ga-prostate-specific-membrane-antigen-11 positron-emission-tomography/computed-tomography for detecting prostate carcinoma in patients with rising prostate-specific-antigen after primary therapy. Six hundred sixty (660) patients with biochemical recurrence referred for positron-emission-tomography/computed-tomography with Ga-prostate-specific-membrane-antig…

Hyperechogenicity of the substantia nigra in healthy controls is related to MRI changes and to neuronal loss as determined by F-Dopa PET

Abstract Transcranial ultrasound (TCS) has been shown to reveal hyperechogenicity of the substantia nigra (SN) in Parkinsonian patients and in about 10% of healthy controls. It is hypothesized that SN hyperechogenicity in healthy subjects is a vulnerability marker for idiopathic Parkinson's disease (IPD). Although there is strong evidence that the echomarker results from increased local iron content, the exact pathophysiological mechanisms remain incompletely understood. Thus, prognostic impact can only be estimated. We examined 14 subjects with SN hyperechogenicity (SN+) (7 IPD patients and 7 controls) and 7 healthy controls without the echomarker (SN−) by a magnetic resonance imaging meth…

High opiate receptor binding potential in the human lateral pain system: A (FEDPN)PET study

Dopamine D2/D3 receptor availability and venturesomeness.

The construct of impulsivity is considered as a major trait of personality. There is growing evidence that the mesolimbic dopamine system plays an important role in the modulation of impulsivity and venturesomeness, the two key components within the impulsivity-construct. The aim of the present study was to explore an association between trait impulsivity measured with self-assessment and the dopaminergic neurotransmission as measured by positron emission tomography (PET) in a cohort of healthy male subjects. In vivo D2/D3 receptor availability was determined with [(18)F]fallypride PET in 18 non-smoking healthy subjects. The character trait impulsivity was measured using the Impulsiveness-V…

Central correlation of muscle sympathetic nerve activation during baroreflex unloading - a microneurography-positron emission tomography study

The baroreceptor reflex controls spontaneous fluctuations in blood pressure. One major control variable of the baroreflex is the sympathetic vasoconstrictor activity to muscles [MSNA; burst frequency (BF) and burst incidence (BI)], which can be quantitatively assessed by microneurography. We aimed to investigate the central regions involved in baroreflex regulation of MSNA. Healthy men (mean age 25 years) participated in three experimental sessions. (i) Microneurography recordings of MSNA from the left peroneal nerve during rest and baroreflex unloading, induced by lower body negative pressure (LBNP; -40 mmHg). If MSNA could be reliably recorded throughout this procedure (n = 15), the subje…

Dual-Time Point [68Ga]Ga-PSMA-11 PET/CT Hybrid Imaging for Staging and Restaging of Prostate Cancer

Routine [68Ga]Ga-PSMA-11 PET/CT (one hour post-injection) has been shown to accurately detect prostate cancer (PCa) lesions. The goal of this study is to evaluate the benefit of a dual-time point imaging modality for the staging and restaging of PCa patients. Biphasic [68Ga]Ga-PSMA-11 PET/CT of 233 patients, who underwent early and late scans (one/three hours post-injection), were retrospectively studied. Tumor uptake and biphasic lesion detection for 215 biochemically recurrent patients previously treated for localized PCa (prostatectomized patients (P-P)/irradiated patients (P-I) and 18 patients suspected of having primary PCa (P-T) were separately evaluated. Late [68Ga]Ga-PSMA-11 PET/CT …

Corrigendum to “The thalamus as the generator and modulator of EEG alpha rhythm: A combined PET/EEG study with lorazepam challenge in humans” [NeuroImage 22 (2004) 637–644]

Department of Psychiatry, Johannes Gutenberg–University Mainz, 55131 Mainz, GermanyAvailable online 2 May 20061053-8119/$ - see front matter D 2006 Elsevier Inc. All rights reserved.doi:10.1016/j.neuroimage.2006.03.007DOI of original article:10.1016/j.neuroimage.2004.01.047.* Corresponding author. Department of Nuclear Medicine, Johannes Gutenberg–University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany. Fax: +496131 17 2448.E-mail address: schreckenberger@nuklear.klinik.uni-mainz.de (M. Schreckenberger).Available online on ScienceDirect (www.sciencedirect.com).

PET Lung Ventilation/Perfusion Imaging Using 68Ga Aerosol (Galligas) and 68Ga-Labeled Macroaggregated Albumin

Pulmonary imaging using ventilation/perfusion (V/P) single-photon emission tomography (V/P scan) with Tc-99m-labeled radiotracers is a well-established diagnostic tool for clinically suspected pulmonary embolism (PE). Ga-68 aerosol (Galligas) and Ga-68-labeled macroaggregated albumin (MAA) are potential tracers for positron emission tomography (PET) lung V/P imaging and could display an advantage over conventional V/P scans in terms of sensitivity and specificity. After radiochemical and animal studies, the clinical applicability of Ga-68 aerosol (Galligas) and Ga-68-labeled MAA was investigated in an exploratory study in patients with clinical suspicion of PE. PET scans were acquired using…

Human dopamine receptor D2/D3 availability predicts amygdala reactivity to unpleasant stimuli

r r Abstract: Dopamine (DA) modulates the response of the amygdala. However, the relation between dopa- minergic neurotransmission in striatal and extrastriatal brain regions and amygdala reactivity to affective stimuli has not yet been established. To address this issue, we measured DA D2/D3 receptor (DRD2/3) availability in twenty-eight healthy men (nicotine-dependent smokers and never-smokers) using positron emission tomography with ( 18 F)fallypride. In the same group of participants, amygdala response to unpleasant visual stimuli was determined using blood oxygen level-dependent (BOLD) functional mag- netic resonance imaging. The effects of DRD2/3 availability in emotion-related brain …

Diagnostic Performance of Multiparametric Magnetic Resonance Imaging and Fusion Targeted Biopsy to Detect Significant Prostate Cancer

Background/aim Multiparametric magnetic resonance imaging combined with ultrasound-fusion-targeted biopsy of the prostate intends to increase diagnostic precision, which has to be clarified. Patients and methods We performed multiparametric magnetic resonance imaging followed by ultrasound-fusion-guided perineal biopsy in 99 male patients with elevated prostate-specific-antigen and previous negative standard biopsy-procedures. Results In 33/99 patients (33%) no malignancy could be confirmed by histopathology. Low-grade carcinomas (Gleason-Score 6+7a) were found in 42/66 (64%) and high-grade carcinomas (Gleason-Score ≥7b) in 24/66 (36%) men. A high-grade carcinoma corresponded to PI-RADS 4 o…

6-18F-Fluoro-l-Dihydroxyphenylalanine Positron Emission Tomography Is Superior to123I-Metaiodobenzyl-Guanidine Scintigraphy in the Detection of Extraadrenal and Hereditary Pheochromocytomas and Paragangliomas: Correlation with Vesicular Monoamine Transporter Expression

Context: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) may be better detected by 18F-fluorodihydroxyphenylalanine-positron emission tomography (FDOPA-PET) than 123I-metaiodobenzyl-guanidine (123-I-MIBG) scintigraphy. Objective: The objective of the study was to correlate functional imaging results with immunohistochemical, molecular-genetic, and biochemical findings. Design and Setting: Thirty consecutive patients with suspected PHEO/PGL presenting at a tertiary referral centre were investigated in a prospective study. Patients: Twenty-five patients had confirmed PHEO/PGL. Thirteen of 25 patients had a hereditary PHEO/PGL syndrome (two multiple endocrine neoplasia II, six succinate de…

Value of Combined PET Imaging with [18F]FDG and [68Ga]Ga-PSMA-11 in mCRPC Patients with Worsening Disease during [177Lu]Lu-PSMA-617 RLT

Despite the promising results of prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) in metastatic castration-resistant prostate cancer (mCRPC), some patients show worsening disease during PSMA-RLT. We investigated the value of combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging in this setting. In n = 29 mCRPC patients with worsening disease after a median of four cycles of [177Lu]Lu-PSMA-617 RLT, combined [18F]FDG and [68Ga]Ga-PSMA-11 PET imaging was performed to detect [18F]FDG-avid lesions with low or no PSMA expression (mismatch lesions). To evaluate prognostic implication of mismatch, survival analyses regarding presence, location, and [18F]FDG PET-derived para…

Small animal tumour imaging with MRI and the ECAT EXACT scanner: application of partial volume correction and comparison with microPET data.

Objective Partial volume effects caused by limited spatial resolution of conventional positron emission tomography (PET) scanners result in an underestimation of the activity concentration in small tumours. The aim of the study was to evaluate the feasibility of small animal tumour imaging with the clinical PET scanner ECAT EXACT after partial volume correction based on MRI calculations. The same tumour model was examined additionally with the small animal PET system, microPET focus 120. Methods Before the ECAT EXACT studies recovery coefficients for different sphere volumes were generated with phantom experiments. For the following in-vivo study DS-sarcoma cells were implanted on both hind…

Diagnostic efficacy of Gallium-68-PSMA PET/CT in 565 patients with biochemical recurrence of prostate cancer

Association of Low Striatal Dopamine D2Receptor Availability With Nicotine Dependence Similar to That Seen With Other Drugs of Abuse

All drugs of abuse induce a phasic dopamine release within the striatum that does not undergo habituation. Prolonged substance consumption impairs the natural function of the mesolimbic dopamine system, as shown by a decrease in the availability of striatal dopamine 2 (D(2)) receptors in patients suffering from cocaine, heroin, amphetamine, and alcohol dependence. However, it is unclear whether similar changes can also be observed in heavy-smoking nicotine-dependent smokers.In vivo D(2)/D(3) receptor availability was determined with [ (18)F]fallypride positron emission tomography in 17 heavy-smoking nicotine-dependent subjects and in 21 age-matched never-smoking comparison subjects. The smo…

18F-fluorodeoxyglucose hypometabolism in cerebellar tonsil and flocculus in downbeat nystagmus.

A patient with downbeat nystagmus was examined by F-fluorodeoxyglucose-positron emission tomography once while off and twice while on successful treatment with 4-aminopyridine. All positron emission tomography scans of the patient showed a reduced cerebral glucose metabolism bilaterally in the region of the cerebellar tonsil and flocculus/paraflocculus when compared with a normal database of the whole brain. An additional region-of-interest analysis revealed that 4-aminopyridine treatment lessened the hypometabolism. This finding supports the hypothesis that the cerebellar tonsil and (para-) flocculus play a crucial role in downbeat nystagmus. The hypometabolism might reflect reduced inhibi…

PSA and PSA kinetics as predictor of a positive Ga-68-PSMA-11 PET/CT scan for restaging prostate cancer